前列腺癌早期诊断的多基因研究
|
摘要
前列腺癌是一个以老年人为主的疾病。其发病率随着年龄的增长而增加,有75%新诊断的前列腺癌病例为65以上的男性。50岁以后,发病率和死亡率均呈指数增长。当前临床诊断中使用血清前列腺特异性抗原(prostate specific antigen, PSA)作为前列腺癌的和前列腺增生的主要鉴别诊断手段。然而由于PSA对PCa并不是特异的,血清PSA浓度升高并非总是提示PCa。当PSA水平轻度升高,在4-10ng/ml之间时,还难以判断是BPH还是早期PCa。并且PSA无法提供肿瘤内在本质信息,也即不能指导临床肿瘤分期,提供治疗和预后的决策信息。前列腺癌的发生是一个多基因渐变失衡的复杂过程,而且肿瘤本身是各种不同性的细胞失衡生长的总称,关联不同信号系统,凭单一指标的检测无法准确判断。近期,人们发现多个基因表达的变化与前列腺癌病程相关,如能结合临床病理学研究,未来可作为前列腺癌病程的生物标记,对前列腺癌进行早期诊断和分型。
本研究拟从多基因入手,研究临床肿瘤基因表达谱特征,寻找比PSA更可靠的临床诊断标记物组合。在国内外关于前列腺癌基因表达谱的研究结果基础上,采用数据挖掘等方法筛选出研究基因,设计目的基因符合荧光定量PCR要求的引物和序列,克隆靶序列到质粒中,以备后期制作标准曲线。同时对收集的临床样本提取RNA,用荧光定量PCR方法分别研究了基因表达变化的表达谱特征和基因组表达比值变化的表达谱特征。第一批选择预选了9个基因(KLK3/PSA、KLK2、KLK11、pim-1、hepsin、PSMA、AR、p27、IGF-1)作为研究对象,通过荧光定量PCR检测临床样本中上述基因的表达变化,结果表明这9个基因组合能明显区分PCa和BPH,其中pim-1、KLK2、PSMA、AR可作为检测基因的核心组合。第二批选择预选了12个基因(trmp-2、RPS16、TMPRSS2、KLK11、Ki-67、PCNA、HER2/ERBB2、MYC、NFKBIA、SREBF2、PSMA/FOLH1、GSTP1),并组合为6组表达比值,通过荧光定量PCR技术,对前列腺癌细胞株(LNCaP和PC-3)、前列腺癌和前列腺增生临床样本的12个基因的6组表达比值进行检测。结果表明TMPRSS2/KLK11、Ki-67/PCNA、NFKBIA/SREBF2比值可作为检测基因的核心组合；而HER2/MYC基因组合虽然没有前列腺癌的特异性,但是HER2/MYC的高表达可能有助于前列腺癌的早期诊断。
Prostate cancer (PCa) is frequently diagnosed in elder men, and its risk is associated with increase of age.75% newly diagnosed PCa are patients with an age of more than 65 years old. The incidence and mortality rates all present an index number growth when men beyond 50 years old. In clinical, the prostate-specific antigen (PSA) has been widely used in screening for prostate cancer. Since PSA elevation is also associated with prostatitis and benign prostatic hyperplasia (BPH), elevated PSA levels do not always indicate the presence of Pca because of its insufficent specificity. In particularly, it is dificult to distinguish PCa between BPH when an individual gets PSA between 4.0 ng/ml and 10.0 ng/ml. And the PSA test can't give the inherent nature of PCa, so not to guide the clinical tumor classification and not to provide the decision-making information of treatment and prognosis. PCa is a multi-gene imbalance in the complex process of gradual change, and diffent clinical PCa may have different gene imbalance and associated with different signal systems, so virtually it is impossible to diagnosis PCa accurately by using a single biomarker. Recent years, a number of genes are reveaed that which expression changes with PCa progression. Forward study these result on clinical pathology; there are promice to develop some bettor biomarkers than PSA for early diagnosis and type of PCa.
Thus, the objective of our research is the identification of more specific and predictive biomarkers for improving clinical management by studing multi-gene expression profile of clinical PCa samples. Harnessing the current research results on gene expression of PCa, target genes are selected by data mining methods, and then the genes'primer and sequence are designed according to FQ-PCR's requirement. FQ-PCR with SYBR Green I are carried out to detect the mRNA expression levels of these genes in clinical samples.
First, to study gene expression, we pre-choose 9 genes (KLK3/PSA、KLK2、KLK11、pim-1、hepsin、PSMA、AR、p27、IGF-1) as a biomarker combination to advance clinical trial on PCa tests. The results showed the PCa and BPH samples can be classified by the 9 genes expression profile, and among the 9 genes, pim-1, KLK2, AR and PSMA have the core contribution to classification. Second, to study gene expression ratio,12 genes (trmp-2、RPS16、TMPRSS2、KLK11、Ki-67、PCNA、HER2、MYC、NFKBIA、SREBF2、PSMA、GSTP1) are selected. The expression ratio result showed the 12 genes expression profile can provide useful imformation for PCa diagonosis, and among the 12 genes, TMPRSS2、KLK11、Ki-67、PCNA、NFKBIA、SREBF2 would be the most potential biomarker combinations. Howerver, HER2/MYC is the non-special gene combination in PCa, its overexpression may contribute to the early detection of PCa.
本研究拟从多基因入手,研究临床肿瘤基因表达谱特征,寻找比PSA更可靠的临床诊断标记物组合。在国内外关于前列腺癌基因表达谱的研究结果基础上,采用数据挖掘等方法筛选出研究基因,设计目的基因符合荧光定量PCR要求的引物和序列,克隆靶序列到质粒中,以备后期制作标准曲线。同时对收集的临床样本提取RNA,用荧光定量PCR方法分别研究了基因表达变化的表达谱特征和基因组表达比值变化的表达谱特征。第一批选择预选了9个基因(KLK3/PSA、KLK2、KLK11、pim-1、hepsin、PSMA、AR、p27、IGF-1)作为研究对象,通过荧光定量PCR检测临床样本中上述基因的表达变化,结果表明这9个基因组合能明显区分PCa和BPH,其中pim-1、KLK2、PSMA、AR可作为检测基因的核心组合。第二批选择预选了12个基因(trmp-2、RPS16、TMPRSS2、KLK11、Ki-67、PCNA、HER2/ERBB2、MYC、NFKBIA、SREBF2、PSMA/FOLH1、GSTP1),并组合为6组表达比值,通过荧光定量PCR技术,对前列腺癌细胞株(LNCaP和PC-3)、前列腺癌和前列腺增生临床样本的12个基因的6组表达比值进行检测。结果表明TMPRSS2/KLK11、Ki-67/PCNA、NFKBIA/SREBF2比值可作为检测基因的核心组合；而HER2/MYC基因组合虽然没有前列腺癌的特异性,但是HER2/MYC的高表达可能有助于前列腺癌的早期诊断。
Prostate cancer (PCa) is frequently diagnosed in elder men, and its risk is associated with increase of age.75% newly diagnosed PCa are patients with an age of more than 65 years old. The incidence and mortality rates all present an index number growth when men beyond 50 years old. In clinical, the prostate-specific antigen (PSA) has been widely used in screening for prostate cancer. Since PSA elevation is also associated with prostatitis and benign prostatic hyperplasia (BPH), elevated PSA levels do not always indicate the presence of Pca because of its insufficent specificity. In particularly, it is dificult to distinguish PCa between BPH when an individual gets PSA between 4.0 ng/ml and 10.0 ng/ml. And the PSA test can't give the inherent nature of PCa, so not to guide the clinical tumor classification and not to provide the decision-making information of treatment and prognosis. PCa is a multi-gene imbalance in the complex process of gradual change, and diffent clinical PCa may have different gene imbalance and associated with different signal systems, so virtually it is impossible to diagnosis PCa accurately by using a single biomarker. Recent years, a number of genes are reveaed that which expression changes with PCa progression. Forward study these result on clinical pathology; there are promice to develop some bettor biomarkers than PSA for early diagnosis and type of PCa.
Thus, the objective of our research is the identification of more specific and predictive biomarkers for improving clinical management by studing multi-gene expression profile of clinical PCa samples. Harnessing the current research results on gene expression of PCa, target genes are selected by data mining methods, and then the genes'primer and sequence are designed according to FQ-PCR's requirement. FQ-PCR with SYBR Green I are carried out to detect the mRNA expression levels of these genes in clinical samples.
First, to study gene expression, we pre-choose 9 genes (KLK3/PSA、KLK2、KLK11、pim-1、hepsin、PSMA、AR、p27、IGF-1) as a biomarker combination to advance clinical trial on PCa tests. The results showed the PCa and BPH samples can be classified by the 9 genes expression profile, and among the 9 genes, pim-1, KLK2, AR and PSMA have the core contribution to classification. Second, to study gene expression ratio,12 genes (trmp-2、RPS16、TMPRSS2、KLK11、Ki-67、PCNA、HER2、MYC、NFKBIA、SREBF2、PSMA、GSTP1) are selected. The expression ratio result showed the 12 genes expression profile can provide useful imformation for PCa diagonosis, and among the 12 genes, TMPRSS2、KLK11、Ki-67、PCNA、NFKBIA、SREBF2 would be the most potential biomarker combinations. Howerver, HER2/MYC is the non-special gene combination in PCa, its overexpression may contribute to the early detection of PCa.
引文
[1]Cancer Trends Progress Report in 2004 (http://progressreport.cancer.gov).
[2]孙颖浩.我国前列腺癌的研究现状[J].中华泌尿外科杂志,2004,25(2)：77-81.
[3]Wong YC, Wang XH, Ling MT. Prostate development and carcinogenesis.Int Rev Cytol.2003; 227:65-130.
[4]Nelson WG, DeWeese TL, DeMarzo AM. The Diet, Prostate Inflammation, and the Development of Prostate Cancer. Cancer and Metastasis Reviews.2002, 21(1):3-16.
[5]Linja MJ, Porkka KP, Kang ZK, etc. Expression of androgen receptor coregulators in prostate cancer. Clin Can Res.,2004,10:1032-1040.
[6]Chen CD, Welsbie DS, Tran C, et al. Molecular determinants of resistance to antiandrogen therapy. Nat Med 2004; 10:33-9.
[7]王怀碧,叶明福.前列腺上皮内瘤的研究进展.诊断病理学杂志,2003；10(5)：307-310.
[8]Porkka KP, Visakorpi T. Molecular mechanisms of prostate cancer. Eur Urol. 2004 Jun;45(6):683-691.
[9]Lessick M, Katz A. A genetics perspective on prostate cancer. Urol Nurs.2006; 26(6):454-60.
[10]Fridman JS, Lowe SW. Control of apoptosis by p53. Oncogene.2003, 22(56):9030-40.
[11]Garner E, Raj K.Protective mechanisms of p53-p21-pRb proteins against DNA damage-induced cell death.Cell Cycle.2008;7(3):277-82.
[12]Maddison LA, Sutherland BW, Barrios RJ, et al. Conditional deletion of Rb causes early stage prostate.Cancer Res.2004; 64(17):6018-25.
[13]Subramanian A, Tamayo P, Mootha VK, et al. Gene set enrichment analysis:A knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sc.2005,102(43):15545-15550.
[14]Edelman EJ, Guinney J, Chi JT, et al. Modeling cancer progression via pathway dependencies. PLoS Comput Biol.2008; 4(2):e28..
[15]Morris DS, Tomlins SA, Rhodes DR, et al. Integrating biomedical knowledge to model pathways of prostate cancer progression. Cell Cycle.2007; 6(10):1177-87.
[16]Sauter ER, Lininger J, Magklara A, et al. Association of kallikrein expression in nipple aspirate fluid with breast cancer risk. Int J Cancer.2004, 108(4):588-91.
[17]Tomlins SA, Rubin MA, Chinnaiyan AM. Integrative biology of prostate cancer progression. Annu Rev Pathol.2006;1:243-71.
[18]金冬雁,黎孟枫等译.分子克隆实验指导(第二版)[M].科学出版社,2000.
[19]Chetcuti A, Margan S, Mann S, et al. Identification of differentially expressed genes in organ-confined prostate cancer by gene expression array. Prostate 2001; 47:132-140.
[20]Bull JH, Ellison G, Patel A, et al. Identification of potential diagnostic markers of prostate cancer and prostatic intraepithelial neoplasia using cDNA microarray. Br J Cancer 2001; 84:1512-1519.
[21]Lessick M, Katz A. A genetics perspective on prostate cancer. Urol Nurs.2006; 26(6):454-60.
[22]Singh D, Febbo PG, Ross K, et al. Gene expression correlates of clinical prostate cancer behavior. Cancer Cell 2002; 1:203-209.
[23]Huppi K, Chandramouli GV. Molecular profiling of prostate cancer. Curr Urol Rep.2004 Feb;5(1):45-51.
[24]邵晨,朱峰,晏伟等.改良消减杂交方法克隆前列腺癌细胞凋亡相关基因.中华泌尿外科杂志.2001,22(8)：479-482.
[25]周利群,杨学贞,黄啸等.应用基因微矩阵芯片筛选前列腺癌的相关基因.中华泌尿外科杂志.2002,23(2)：72-75.
[26]Attard G, Ang JE, Olmos D, et al. Dissecting prostate carcinogenesis through ETS gene rearrangement studies:implications for anticancer drug development. J Clin Pathol.2008; 61(8):891-6.
[27]Tomlins S, Mehra R, Rhodes D, et al. Integrative molecular concept modeling of prostate cancer progression. Nat Genet.2007;39:41-51.
[28]Aerts JL, Gonzales MI, Topalian SL. Selection of appropriate control genes to assess expression of tumor antigens using real-time RT-PCR. Biotechniques. 2004; 36(1):84-6,88,90-1.
[29]Vandesompele J, De Paepe A, Speleman F. Elimination of primer-dimer artifacts and genomic coamplification using a two-step SYBR green I real-time RT-PCR. Anal Biochem.2002; 303(1):95-8.
[30]Jeong YJ, Choi HW, Shin HS, et al. Optimization of real time RT-PCR methods for the analysis of gene expression in mouse eggs and preimplantation embryos. Mol Reprod Dev.2005; 71(3):284-9.
[31]Bengtsson M, Karlsson HJ, Westman G, Kubista M. A new minor groove binding asymmetric cyanine reporter dye for real-time PCR. Nucleic Acids Res, 2003,31(8):e45.
[32]Richardson TD, Oesterling JE. Age-specific reference ranges for serum prostate-specific antigen.Urol Clin North Am.1997; 24(2):339-51.
[33]Moroy T, Grzeschiczek A, Petzold S, et al. Expression of a PIM-1 transgene accelerates lymphoproliferation and inhibits apoptosis in lpr/lpr mice. Proc Natl Acad Sci USA,1993,90(22):10743-10748.
[34]Wang ZP, Nandini, Matt W, et al. PIM-1 a serine/threonine kinase with a role in cell survival, proliferation, differentiation and tumorigenesis]. Vet Sci,2001, 2(3):167-169.
[35]Leverson JD, Koskinen PJ, Orrico FC, et al. PIM-1 kinase and p100 cooperate to enhance c-Myb activity. Mol Cell,1998 2(4):417-425.
[36]Thompson J, Peltola KJ, Koskinen PJ, et al. Attenuation of androgen receptor-dependent transcription by serine/threonine kinase PIM-1. Lab Invest, 2000,83(9):1301-1309.
[37]翁迈,周利群,王建伟,等.PIM-1蛋白激酶在前列腺癌组织中的表达.基础医学与临床,2005,25：503-506
[38]张彤,徐勇,张淑敏,等.PIM-1在前列腺癌组织中的表达及与血清PSA的关系.中国男科学杂志,2005,19：19-21.
[39]Alexander Valdman, Xiaolei Fang, See-Tong Pang, et al.PIM-1 expression in prostatic intraepithelial neoplasia and human prostate cancer [J]. Prostate, 2004,60:367-371.
[40]钟惟德,李俊玲,何慧婵,等.实时荧光定量TR-PCR检测良性前列腺增生与前列腺癌相关基因表达的临床意义.中华泌尿外科杂志,2005,26：615-618.
[41]Obiezu CV, Diamandis EP. Human tissue kallikrein gene family:applications in cancer. Cancer Lett,2005,224(1):1-22
[42]Magklara A, Scorias A, Lopen-OtinC, et al. Human Glandular Kallikrein in Breast Milk, Antiniotic Fluid and Breast Cyst Fluid. Clin Chem, 1999,45:1774-1780.
[43]Rittenhous HG, Finlay JA, Mikolaajczyk SD, et al. Human Kallikrein2(hK2)and Prostate Specific Antigen(SPA):How Closely Related, but District Kallikreins in the Prostate. Crit Rev Clin Lab Sci,1998,35:275-368.
[44]Becker C, Piironen T, Pettersson K, et al. Clinical value of human glandular kallikrein 2 and free and total prostate-specific antigen in serum from a population of men with prostate-specific antigen levels 3.0 ng/mL or greater. Urology,2000,55(5):694-9.
[45]So A, Goldenberg L, Gleave ME. Prostate specific antigen:an updated review. Can J Urol,2003,10(6):2040-50.
[46]曾浩,李虹,张秀辉,等.前列腺特异性膜抗原表达的临床意义.中华泌尿外科杂志,2003,6：392-394.
[47]Wilson CM, McPhaul MJ. A and B forms of the androgen re2ceptor are present in human genital skin fibroblasts. ProcNatl Acad Sci USA,1994,91(4):1234-1238.
[48]Brolin J,Skoog l,Ekman P.Immunohhistochemistry and biochemistyy in detection of androgen, progesterone,and estrogen receptors in benign and malignant human prostate tissue.Prostate,1992;20940:281-283
[49]Lu ML, Schneider MC, Zheng Y, et al. Caveolin21 interacts with androgen receptor. A positive modulator of androgen receptor mediated transactivation. J Biol Chem,2001,276:13442213451.
[50]Sweat SD.Pacelli A, Bergstralh E, Slezak J. Bostwick D Androgen receptor expression in prostatic intraepithelial neoplasia and cancer, J Urol,1999; 161(4);1229-1232.
[51]Ma XJ, Hilsenbeck SG, Wang W, et al. The HOXB13:IL17BR expression index is a prognostic factor in early-stage breast cancer. J Clin Oncol. 2006;24(28):4611-9.
[52]Ma XJ, Wang Z, Ryan PD, et al. A two-gene expression ratio predicts clinical outcome in breast cancer patients treated with tamoxifen.
[53]Reed CE, Graham A, Hoda RS, et al. A simple two-gene prognostic model for adenocarcinoma of the lung. J Thorac Cardiovasc Surg.2008;135(3):627-34.
[54]Wang X, Li X, Currie R.W, Willette RN, Barone FC, Feuerstein G.Z. Application of real-time polymerase chain reaction to quantitate induced expression of interleukin-lbeta mRNA in ischemic brain tolerance. J Neurosci Res.2000 Jan 15; 59(2):238-46.
[55]Diamandis EP, Yousef GM, Luo LY, Maqklara A, Obiezu CV. The new human kallikrein gene family:implications in carcinogenesis[J].Trends EndocrinolMetab,2000,11 (2):54-60.
[56]Yousef GM, Diamandis EP. The new human tissue kallikrein gene family: structure, function, and association to disease[J]. Endocr Revl2001,22 (2) 184-204.
[57]Diamandis EP, Yousef GM. Human tissue kallikreins:a family of new cancer biomarkers[J]. Clin Chem,2002, Aug;48(8):1198-205.
[58]Paliouras M, Borgono C, Diamandis EP. Human tissue kallikreins:The cancer biomarker family. Cancer Lett.2007 Apr 28;249(1):61-79.
[59]Lin B, Ferguson C, White JT, Wang S, Vessella R, True LD, Hood L, Nelson PS.Prostate-localized and Androgen-regulated Expression of the Membrane-bound Serine Protease TMPRSS2[J]. CANCER RESEARCH,1999, 59(17):4180-4184.
[60]Afar DE, Vivanco I, Hubert RS, Kuo J, Chen E, Saffran DC, Raitano AB, Jakobovits A. Catalytic cleavage of the androgen-regulated TMPRSS2 protease results in its secretion by prostate and prostate cancer epithelia. Cancer Res. 2001 Feb 15;61(4):1686-1692.
[61]Gan L, Lee I, Smith R, Argonza-Barrett R, Lei H, McCuaig J, Moss P, Paeper B, Wang K. Sequencing and expression analysis of the serine protease gene cluster located in chromosome 19q13 region[J]. Gene.2000 Oct 17;257(1):119-30.
[62]Scorilas A, Gregorakis AK. mRNA expression analysis of human kallikrein 11 (KLK11) may be useful in the discrimination of benign prostatic hyperplasia from prostate cancer after needle prostate biopsy[J]. Biol Chem.2006 Jun;387(6):789-793.
[63]Nakamura T, Stephan C, Scorilas A, Yousef GM, Jung K, Diamandis EP. Quantitative analysis of hippostasin/KLK11 gene expression in cancerous and noncancerous prostatic tissues[J]. Urology.2003 May;61(5):1042-1046.
[64]Morris GF, Mathews MB. Regulation of proliferating cell nuclear antigen during the cell cycle[J]. J Biol Chem,1989,264:13856.
[65]Brabo R,Macdonalc, bravo H. Existense of two populations of cyclin/ proliferating cell nuclear antigen during the cell cycle:association with DNA replication sites [J]. J Cell Biol,1987,105 (4):1549.
[66]Chapel F, Guettier C, Chastang C, Rached AA, Mathieu D, Tepper M, Beaugrand M, Trinchet JC. Needle biopsy of hepatocellular carcinoma: assessment of prognostic contribution of histologic parameters including proliferating cell nuclear antigen labeling and correlations with clinical outcomes. Group d'Etude et de Traitement du Carcinoma Hepatocellulaire[J]. Cancer.1996 Mar 1;77(5):864-71.
[67]董昌元,王玲,王贤明,易建华,姚启盛.前列腺癌组织中PCNA、MVD表达与彩超血流检测的研究[J].中国临床医学影像杂志,2007,18(1)：56-58.
[68]孙衍增,牛兆山.P53蛋白和增殖细胞核抗原在前列腺癌中的表达及意义[J].青岛大学医学院学报,2001,37(4)：309-311.
[69]郭琳琅.增殖细胞核抗原在前列腺疾病中的表达及意义[J].临床泌尿外科杂志,1997,12：302.
[70]Nemoto R, Kawamura H, Miyakawa I, Uchida K, Hattori K, Koiso K, Harada M.. Immunohistochemical detection of proliferating cell nuclear antigen (PCNA)/cyclin in human prostate adenocarcinoma [J]. J Urol,1993,149:165
[71]阎洪涛,龚百生,廖勇,杨红,陈照祥.前列腺癌p53和PCNA表达的相关性研究[J].四川医学,2005,26(4)：429-430.
[72]龚百生,阎洪涛,廖勇,杨红,陈照祥.前列腺癌PSA和PCNA表达的相关性研究[J].临床泌尿外科杂志,2006,21(3)：167-170.
[73]朱德茂,杨志,聂长庆.前列腺癌术前细针穿刺涂片的PCNA表达及意义[J].中国肿瘤临床与康复,2002,9(5)：26-27.
[74]Spires S E,Banks E R,Davey D D. Proliferating ell nuclear antigen in prostatic adenocarcinoma:correlation with established prognostic indicators [J]. Urology,1994,43 (5):660.
[75]Gerdes J, Schwab U, Lemke H, Stein H. Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation [J]. Int J Cancer,1983,31(1):13-20.
[76]Charpin C, Dicaire MJ, Barbeau B, Lavaut MN, Andonian C, Devictor B, Allasia C, Bonnier P, Mandeville R. Monoclonal 3C6F9 distribution in human breast carcinomas:image cytometry of immunocytochemical assays[J]. Med Oncol Tumor Pharmacother,1991,8(4):243-251.
[77]Halvorsen OJ, Haukaa S, Hoisaeter PA, Akslen LA.. Maximum Ki-67 staining in prostate cancer provides indepent prognostic information after radical prostatectomy [J]. Anticancer Res,2001,21 (6A):4071-4076.
[78]Munoz E, Gomez F, Paz JI, Casado I, Silva JM, Corcuera MT, Alonso MJ. Ki-67 immunolabeling in pre-malignant lesions and carcinoma of the prostate. Histologic correlation and prognostic evaluation[J]. Eur J Histochem,2003,47 (2):123-128.
[79]Claudio PP, Zamparelli A, Garcia FU, Claudio L, Ammirati G, Farina A, Bovicelli A, Russo G, Giordano GG, McGinnis DE, Giordano A, Cardi G. Expression of Cell-cycle-regulated Protein PRb2/P130, P107, P27-kipl, P53, mdm-2, and Ki-67(MIB-1) in prostatic gland adenocarcinoma[J]. Clin Cancer Res,2002,8(6):1808-1815.
[80]刘喜波,孟春琴.Ki-67和CK34PE12在前列腺癌鉴别诊断中的应用[J].肿瘤研究与临床,2005,17(3)：187-188.
[81]Bantis A, Giannopoulos A, Gonidi M, Liossi A, Aggelonidou E, Petrakakou E, Athanassiades P, Athanassiadou P. Expression of P120,Ki-67and PCNA as proliferation biomarkers in imprint smears of prostate carcinoma and their prognostic smears of prostate carcinoma and their prognostic value. Cytopathology.2004 Feb;15(1):25-31.
[82]8Scherer DC, Brockman JA, Chen Z, Maniatis T, Ballard DW. Signal-induced degradation of I kappa B alpha requires site-specific ubiquitination[J]. Proc Natl Acad Sci U S A.1995,92(24):11259-63.
[83]Johnson MI, Hamdy FC. Apoptosis regulating genes in prostate cancer[J]. Oncol Rep,1998,5(3):553-7.
[84]Karan D, Lin MF, Johansson SL, Batra SK. Current status of the molecular genetics of human prostatic adenocarcinomas[J]. Int J Cancer,2003,103(3): 285-93.
[85]Chen F, Castranova V, Shi X. New insights into the role of nuclear factor-B in cell growth regulation[J]. Am J Pathol,2001,159:387-97.
[86]Gilmore TD. The Rel/NF-B/I B signal transduction pathway and cancer[J]. Cancer Treat Res,2003,115:241-65.
[87]Pfitzenmaier J, Vessella R, Higano CS, Nnteboom JL, Wallace D Jr, Corey E. Elevation of cytokine levels in cachectic patients with prostate carcinoma[J]. Cancer,2003,97(5):1211-6.
[88]Shukla S, Gupta S. Suppression of constitutive and tumor necrosis factor alpha-induced nuclear factor (NF)-kappaB activation and induction of apoptosis by apigenin in human prostate carcinoma PC-3 cells:correlation with down-regulation of NF-kappaB-responsive genes[J]. Clin Cancer Res.2004,10(9): 3169-78.
[89]D. Horton, J.L. Goldstein and M.S. Brown, SREBPs:activators of the complete program of cholesterol and fatty acid synthesis in the liver[J]. J. Clin. Invest. 2002,109(9):1125-1131.
[90]Swinnen JV, Heemers H, van de Sande T, de Schrijver E, Brusselmans K, Heyns W, Verhoeven G. Androgens, lipogenesis and prostate cancer[J]. J Steroid Biochem Mol Biol.2004,92(4):273-9.
[91]Marmor MD, Skaria KB, Yarden, Y. Signal transduction and oncogenesis by ErbB/HER receptors[J]. Int J Radiat Oncol Biol Phys,2004,58(3):903-13.
[92]陈立勇,郭宁.HER2参与的基因表达调控[J].生物技术通讯,2006,3(17)：398-401.
[93]Galmozzi E, Casalini P, Iorio MV, Casati B, Olqiati C, Menard S. HER2 signaling enhances 5'-UTR-mediated translation of c-Myc mRNA[J]. J Cell Physiol,2004,200 (1):82-8.
[94]曾益新主编.肿瘤学[M].人民卫生出版社,2003.
[95]Livak KJ, SchmittgenTD. Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2-ΔΔCT Method. Methods.2001; 25:402-408.
[96]杨光华.肿瘤病理学[M].第五版.北京人民卫生出版社2000.107-121
[97]王建业.前列腺疾病与临床实践[M].北京出版社2002.229
[98]Yousef GM,Luol-Y, D iamandis E P.Indentification of novel human kallikrein-like genes on chromosome 19q13.3-19q13.4[J] Aticancer Res,1999,19: 2843-2852.
[99]Diamandis EP, Yousef GM. Human tissue kallikreins:a family of new cancer biomarkers[J].Clin Chem,2002,48:1198-1205.
[100]Myers SA, Clements JA. Kallikrein-4(KLK4), a new member of the human kallikrein gene family up-regulated by estrogen and progesterone in the human endometrial cancer cell line[J]. KLEJ Clin Endocrinol Metab, 2001,86:2323-2326.
[101]ChristinaV. Obiezu, Andreas Scorilas, Dionyssios Katsaros. Higher human kallikrein gene 4 expression indicates poor prognosis os ovarian cancer
patients[J]. Clinical cancer research,2001,7:2380-2386.
[102]董志伟.中国癌症研究进展——中国主要癌症的筛查及早诊早治[M].北京大学医学出版社,2004,12：252.
[103]Wang MC, Murphy GP, Chu TM. Purification of a human prostate specific antigen[J]. Invest Urol,1979:159-163.
[104]Stenner J, Holthaus K, Mackenzie SH, Crawford ED. The effect of ejaculation on prostate-specific antigen in a prostate cancer-screening population[J]. Urology,1998,51(3):455-459.
[105]张华,许叔祥.定量聚合酶链反应的研究进展与临床应用[J].中华检验医学杂志,2000,23(2)：120-121.
[106]Schweitzer B, Kingsmore S. Combining nucleic acid amplification and detection[J]. Current Opinions in Biotechnology,2001,12:21-27.
[107]Eis PS, Olson MC, Takova T, Curtis ML, Olson SM, Vener TI, Ip HS, Vedvik KL, Bartholomay CT, Allawi HT, Ma WP, Hall JG, Morin MD, Rushmore TH, Lyamichev VI, Kwiatkowski RW. An invasive cleavage assay for direct quantitation of specific RNAs[J]. Nature Biotechnology,2001,19:673-676.
[108]Klein D. Quantification using real-time PCR technology:applications and limitations[J]. TRENDS in Molecular Medicine,2002,8:257-259.
[109]Bonnet G, Tyagi S, Libchaber A, Kramer FR. Thermodynamic basis of the enhanced specificity of structured DNA probes[J]. PNAS,1999, 96:6171-6176.
[110]Gut M, Leutenegger CM, Huder JB, Pedersen NC, Lutz H.. One-tube fluorogenic reverse transcription-polymerase chain reaction for the quantitation of feline coronaviruses[J]. Journal of Virological Methods,1999, 77:37-46.
[111]Tyagi S, Kramer FR. Molecular beacons:probes that fluoresce upon hybridization[J]. Nature Biotechnology,1996,14:303-308.
[112]Taveau M, Stockholm D, Spencer M, Richard I. Taveau M, Stockholm D, Spencer M. Quantification of splice variants using molecular beacon or scorpion primers[J]. Anal Biochem.2002 Jun 15;305(2):227-35.
[113]Rickert AM, Borodina TA, Kuhn EJ, Lehrach H, Sperling S..Refinement of single-nucleotide polymorphism genotyping methods on human genomic DNA:amplifluor allele-specific polymerase chain reaction versus ligation detection reaction-TaqMan[J]. Analytical Biochemistry 2004;330:288-297.
[114]Saha BK, Tian B, Bucy RP. Quantitation of HIV-1 by real-time PCR with a unique fluorogenic probe[J]. J Virol Met 2001;93:33-42.
[115]施林祥,李东辉.实时荧光PCR研究新进展[J].世界华人消化杂志,2005,13(5)596-599.
[116]袁媛,陈强,陈思祗,刘中来.实时荧光定量PCR技术及其在生命科学领域中的应用(一)[J].海峡预防医学杂志,2006,12(4)：18-20.
[117]Pryor RJ, Wittwer CT. Real-time polymerase chain reaction and melting curve analysis[J]. Methods Mol Biol.2006;336:19-32.
[118]Bustin S. transcription absolute quantification of mRNA using real-time reverse
[119]polymerase chain reaction assays [J]. J Mol Endocrinol,2000,25:169-193.
[120]Sellars MJ, Vuocolo T, Leeton LA, Coman GJ, Degnan BM, Preston NP. Real-time RT-PCR quantification of Kuruma shrimp transcripts:A comparison of relative and absolute quantification procedures [J]. J Biotechnol.2007 Feb 9
[121]Leong DT, Gupta A, Bai HF, Wan G, Yoong LF, Too HP, Chew FT, Hutmacher DW. Absolute quantification of gene expression in biomaterials research using real-time PCR[J]. Biomaterials.2007 Jan;28(2):203-10.
[122]Bustin SA. Absolute quantification of mRNA using real-time reverse transcription polymerase chain reaction assays [J]. J Mol Endocrinol, 2000,25(2):169-193.
[123]Giulietti A, Overbergh L, Valckx D, Decallonne B, Bouillon R, Mathieu C. An overview of real-time quantitative PCR:applications to quantify cytokine gene expression[J]. Methods,2001,25(4):386-401.
[124]张燕,沈茜.一种快速构建cRNA标准曲线检测基因表达方法的建立[J].生物化学与生物物理进展,2003,30(3)：474-477.
[125]张弛宇,徐顺高,黄新祥.一种新颖简便的荧光实时RT-PCR相对定量方法的建立[J].生物化学与生物物理进展,2005,32(9)：883-888.
[126]Aliyu SH, Aliyu MH, Salihu HM, Parmar S, Jalal H, Curran MD. Rapid detection and quantitation of hepatitis B virus DNA by real-time PCR using a new fluorescent (FRET) detection system[J].J Clin Virol.2004 Jun;30(2):191-5.
[127]Singh M, Dicaire A, Wakil AE, Luscombe C, Sacks SL. Quantitation of hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) in the liver of HBV-infected patients by LightCycler real-time PCR[J]. J Virol Methods. 2004 Jun 15; 118(2):159-67.
[128]D.L.斯佩克特,R.D.戈德曼,L.A.莱因万德.细胞实验指南(上册)[M].科学出版社,2001.
[129]Donald S Coffey. Prostate cancer:an overview of increasing dilemma[J]. Cancer,1993,71:880-886.
[130]Maliner-Stratton M S, Klein R D,Udayakumar T S, Nagle RB, Bowden GT. Interleukin-1 beta-induced promatrilysin expression is mediated by NFkappaB-regulated synthesis of interleukin-6 in the prostate carcinoma cell line, LNCaP.Neoplasia.2001,3(6):509-20.
[131]Murphy GP. Models for prostate cancer[M]. New York:Liss; 1980:115-132.
[132]Kaighn ME, Narayan KS, Ohnuki Y, Lechner JF, Jones LW. Establishment and characterization of a human prostatic carcinoma cell line (PC-3)[J]. Invest. Urol.17:16-23,1979.
[133]Grossmann ME, Huang H, Tindall DJ. Androgen receptor signaling in androgen-refractory prostate cancer[J]. J Natl Cancer Inst,2001,93(22): 1687-1697.
[134]Feldman BJ, Feldman D. The development of androgen-independent prostate cancer[J]. Nat Rev Cancer,2001,1(1):34-45.
[135]A de la Taille, F Vacherot, L Salomon, C Drue, S Gil Diez de Medina, C Abbou, R Buttyan, D Chopin. Hormone-refractory prostate cancer:a multi-step and multi-event process[J]. Prostate Cancer Prostatic Dis, 2001,4(4):204-212.
[136]Zhao H, Kim Y, Wang P, Lapointe J, Tibshirani R, Pollack JR, Brooks JD. Genome-Wide Characterization of Gene Expression Variations and DNA Copy Number Changes in prostate Cancer Cell Lines. The Prostate 63:187-197 (2005).
[137]金冬雁,黎孟枫等译.分子克隆实验指导(第二版)[M].科学出版社,2000.
[138]Bengtsson M, Karlsson HJ, Westman G, Kubista M. A new minor groove binding asymmetric cyanine reporter dye for real-time PCR[J]. Nucleic Acids Res,2003,31 (8):e45.
[139]Espy MJ, Uhl JR, Sloan LM, Buckwalter SP, Jones MF, Vetter EA, Yao JD, Wengenack NL, Rosenblatt JE, Cockerill FR 3rd, Smith TF. Real-time PCR in clinical microbiology:applications for routine laboratory testing. Clin Microbiol Rev.2006 Jan; 19(1):165-256.
[140]Bustin SA. Absolute quantification of mRNA using real-time reverse transcription polymerase chain reaction assays[J]. Molecular Endocrinology, 2000,25:169.
[141]Wang X, Li X, Currie R.W, Willette RN, Barone FC, Feuerstein G.Z. Application of real-time polymerase chain reaction to quantitate induced expression of interleukin-lbeta mRNA in ischemic brain tolerance. J Neurosci Res.2000 Jan 15; 59(2):238-46.
[142]de Kok JB, Ruers TJ, van Muijen GN, van Bokhoven A, Willems HL, Swinkels DW. Real-time quantification of human telomerase reverse transcriptase mRNA in tumors and healthy tissues. Clin Chem.2000 Mar;46(3):313-8.
[143]Moody A, Sellers S, Bumstead N. Measuring infectious bursal disease virus RNA in blood by multiplex real-time quantitative RT-PCR[J]. Virol. Methods,2000,Mar; 85(1-2):55-64.
[144]钟惟德,李俊玲,何慧婵,江福能,刘文华,毕学成,彭志强,刘良式,魏鸿蔼.实时荧光定量RT-PCR检测良性前列腺增生与前列腺癌相关基因表 达的临床意义[J].中华泌尿外科杂志,2005,26(9)：615-618.
[145]Ostrander EA, Stanford JL. Genetics of prostate cancer:too many loci, too few genes. Am J Hum Genet,2000,Dec; 67(6):1367-1375.
[146]Diamandis EP, Yousef GM, Luo LY, Maqklara A, Obiezu CV. The new human kallikrein gene family:implications in carcinogenesis[J].Trends EndocrinolMetab,2000,11 (2):54-60.
[147]Yousef GM, Diamandis EP. The new human tissue kallikrein gene family: structure, function, and association to disease[J]. Endocr Revl2001,22 (2) 184-204.
[148]Diamandis EP, Yousef GM. Human tissue kallikreins:a family of new cancer biomarkers[J]. Clin Chem,2002, Aug;48(8):1198-205.
[149]Paliouras M, Borgono C, Diamandis EP. Human tissue kallikreins:The cancer biomarker family. Cancer Lett.2007 Apr 28;249(1):61-79.
[150]Lin B, Ferguson C, White JT, Wang S, Vessella R, True LD, Hood L, Nelson PS. Prostate-localized and Androgen-regulated Expression of the Membrane-bound Serine Protease TMPRSS2[J]. CANCER RESEARCH, 1999,59(17):4180-4184.
[151]Afar DE, Vivanco I, Hubert RS, Kuo J, Chen E, Saffran DC, Raitano AB, Jakobovits A. Catalytic cleavage of the androgen-regulated TMPRSS2 protease results in its secretion by prostate and prostate cancer epithelia. Cancer Res.2001 Feb 15;61(4):1686-1692.
[152]Gan L, Lee I, Smith R, Argonza-Barrett R, Lei H, McCuaig J, Moss P, Paeper B, Wang K. Sequencing and expression analysis of the serine protease gene cluster located in chromosome 19q13 region[J]. Gene.2000 Oct 17;257(1):119-30.
[153]Scorilas A, Gregorakis AK. mRNA expression analysis of human kallikrein 11 (KLK11) may be useful in the discrimination of benign prostatic hyperplasia from prostate cancer after needle prostate biopsy[J]. Biol Chem.2006 Jun;387(6):789-793.
[154]Nakamura T, Stephan C, Scorilas A, Yousef GM, Jung K, Diamandis EP. Quantitative analysis of hippostasin/KLK11 gene expression in cancerous and noncancerous prostatic tissues[J]. Urology.2003 May;61(5):1042-1046.
[155]Morris GF, Mathews MB. Regulation of proliferating cell nuclear antigen during the cell cycle[J]. J Biol Chem,1989,264:13856.
[156]Brabo R,Macdonalc, bravo H. Existense of two populations of cyclin/ proliferating cell nuclear antigen during the cell cycle:association with DNA replication sites [J]. J Cell Biol,1987,105 (4):1549.
[157]Chapel F, Guettier C, Chastang C, Rached AA, Mathieu D, Tepper M, Beaugrand M, Trinchet JC. Needle biopsy of hepatocellular carcinoma: assessment of prognostic contribution of histologic parameters including proliferating cell nuclear antigen labeling and correlations with clinical outcomes. Group d'Etude et de Traitement du Carcinoma Hepatocellulaire[J]. Cancer.1996 Mar 1;77(5):864-71.
[158]董昌元,王玲,王贤明,易建华,姚启盛.前列腺癌组织中PCNA、MVD表达与彩超血流检测的研究[J].中国临床医学影像杂志,2007,18(1)：56-58.
[159]孙衍增,牛兆山.P53蛋白和增殖细胞核抗原在前列腺癌中的表达及意义[J].青岛大学医学院学报,2001,37(4)：309-311.
[160]郭琳琅.增殖细胞核抗原在前列腺疾病中的表达及意义[J].临床泌尿外科杂志,1997,12：302.
[161]Nemoto R, Kawamura H, Miyakawa I, Uchida K, Hattori K, Koiso K, Harada M.. Immunohistochemical detection of proliferating cell nuclear antigen (PCNA)/cyclin in human prostate adenocarcinoma [J]. J Urol,1993,149:165
[162]阎洪涛,龚百生,廖勇,杨红,陈照祥.前列腺癌p53和PCNA表达的相关性研究[J].四川医学,2005,26(4)：429-430.
[163]龚百生,阎洪涛,廖勇,杨红,陈照祥.前列腺癌PSA和PCNA表达的相关性研究[J].临床泌尿外科杂志,2006,21(3)：167-170.
[164]朱德茂,杨志,聂长庆.前列腺癌术前细针穿刺涂片的PCNA表达及意义[J].中国肿瘤临床与康复,2002,9(5)：26-27.
[165]Spires S E,Banks E R,Davey D D. Proliferating ell nuclear antigen in prostatic adenocarcinoma:correlation with established prognostic indicators [J]. Urology,
[166]1994,43 (5):660.
[167]Gerdes J, Schwab U, Lemke H, Stein H. Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation [J]. Int J Cancer,1983,31(1):13-20.
[168]Charpin C, Dicaire MJ, Barbeau B, Lavaut MN, Andonian C, Devictor B, Allasia C, Bonnier P, Mandeville R. Monoclonal 3C6F9 distribution in human breast carcinomas:image cytometry of immunocytochemical assays[J]. Med Oncol Tumor Pharmacother,1991,8(4):243-251.
[169]Halvorsen OJ, Haukaa S, Hoisaeter PA, Akslen LA.. Maximum Ki-67 staining in prostate cancer provides indepent prognostic information after radical prostatectomy [J]. Anticancer Res,2001,21 (6A):4071-4076.
[170]Munoz E, Gomez F, Paz JI, Casado I, Silva JM, Corcuera MT, Alonso MJ. Ki-67 immunolabeling in pre-malignant lesions and carcinoma of the prostate. Histologic correlation and prognostic evaluation[J]. Eur J Histochem,2003,47 (2):123-128.
[171]Claudio PP, Zamparelli A, Garcia FU, Claudio L, Ammirati G, Farina A, Bovicelli A, Russo G, Giordano GG, McGinnis DE, Giordano A, Cardi G. Expression of Cell-cycle-regulated Protein PRb2/P130, P107, P27-kipl, P53, mdm-2, and Ki-67(MIB-1) in prostatic gland adenocarcinoma[J]. Clin Cancer Res,2002,8(6):1808-1815.
[172]刘喜波,孟春琴.Ki-67和CK34βE12在前列腺癌鉴别诊断中的应用[J].肿瘤研究与临床,2005,17(3)：187-188.
[173]Bantis A, Giannopoulos A, Gonidi M, Liossi A, Aggelonidou E, Petrakakou E, Athanassiades P, Athanassiadou P. Expression of P120,Ki-67and PCNA as proliferation biomarkers in imprint smears of prostate carcinoma and their prognostic smears of prostate carcinoma and their prognostic value. Cytopathology.2004 Feb;15(1):25-31.
[174]Scherer DC, Brockman JA, Chen Z, Maniatis T, Ballard DW. Signal-induced degradation of I kappa B alpha requires site-specific ubiquitination[J]. Proc Natl Acad Sci U S A.1995,92(24):11259-63.
[175]Johnson MI, Hamdy FC. Apoptosis regulating genes in prostate cancer[J]. Oncol Rep,1998,5(3):553-7.
[176]Karan D, Lin MF, Johansson SL, Batra SK. Current status of the molecular genetics of human prostatic adenocarcinomas[J]. Int J Cancer,2003,103(3): 285-93.
[177]Chen F, Castranova V, Shi X. New insights into the role of nuclear factor-κB in cell growth regulation[J]. Am J Pathol,2001,159:387-97.
[178]Gilmore TD. The Rel/NF-κB/IκB signal transduction pathway and cancer[J]. Cancer Treat Res,2003,115:241-65.
[179]Pfitzenmaier J, Vessella R, Higano CS, Nnteboom JL, Wallace D Jr, Corey E. Elevation of cytokine levels in cachectic patients with prostate carcinoma[J]. Cancer,2003,97(5):1211-6.
[180]Shukla S, Gupta S. Suppression of constitutive and tumor necrosis factor alpha-induced nuclear factor (NF)-kappaB activation and induction of apoptosis by apigenin in human prostate carcinoma PC-3 cells:correlation with down-regulation of NF-kappaB-responsive genes[J]. Clin Cancer Res. 2004,10(9):3169-78.
[181]D. Horton, J.L. Goldstein and M.S. Brown, SREBPs:activators of the complete program of cholesterol and fatty acid synthesis in the liver [J]. J. Clin. Invest.2002,109(9):1125-1131.
[182]Swinnen JV, Heemers H, van de Sande T, de Schrijver E, Brusselmans K, Heyns W, Verhoeven G. Androgens, lipogenesis and prostate cancer[J]. J Steroid Biochem
[183]Mol Biol.2004,92(4):273-9.
[184]Marmor MD, Skaria KB, Yarden, Y. Signal transduction and oncogenesis by ErbB/HER receptors[J]. Int J Radiat Oncol Biol Phys,2004,58(3):903-13.
[185]陈立勇,郭宁.HER2参与的基因表达调控[J].生物技术通 讯,2006,3(17)：398-401.
[186]Galmozzi E, Casalini P, Iorio MV, Casati B, Olqiati C, Menard S. HER2 signaling enhances 5'-UTR-mediated translation of c-Myc mRNA[J]. J Cell Physiol,2004,200 (1):82-8.
[187]曾益新主编.肿瘤学[M].人民卫生出版社,2003.
[2]孙颖浩.我国前列腺癌的研究现状[J].中华泌尿外科杂志,2004,25(2)：77-81.
[3]Wong YC, Wang XH, Ling MT. Prostate development and carcinogenesis.Int Rev Cytol.2003; 227:65-130.
[4]Nelson WG, DeWeese TL, DeMarzo AM. The Diet, Prostate Inflammation, and the Development of Prostate Cancer. Cancer and Metastasis Reviews.2002, 21(1):3-16.
[5]Linja MJ, Porkka KP, Kang ZK, etc. Expression of androgen receptor coregulators in prostate cancer. Clin Can Res.,2004,10:1032-1040.
[6]Chen CD, Welsbie DS, Tran C, et al. Molecular determinants of resistance to antiandrogen therapy. Nat Med 2004; 10:33-9.
[7]王怀碧,叶明福.前列腺上皮内瘤的研究进展.诊断病理学杂志,2003；10(5)：307-310.
[8]Porkka KP, Visakorpi T. Molecular mechanisms of prostate cancer. Eur Urol. 2004 Jun;45(6):683-691.
[9]Lessick M, Katz A. A genetics perspective on prostate cancer. Urol Nurs.2006; 26(6):454-60.
[10]Fridman JS, Lowe SW. Control of apoptosis by p53. Oncogene.2003, 22(56):9030-40.
[11]Garner E, Raj K.Protective mechanisms of p53-p21-pRb proteins against DNA damage-induced cell death.Cell Cycle.2008;7(3):277-82.
[12]Maddison LA, Sutherland BW, Barrios RJ, et al. Conditional deletion of Rb causes early stage prostate.Cancer Res.2004; 64(17):6018-25.
[13]Subramanian A, Tamayo P, Mootha VK, et al. Gene set enrichment analysis:A knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sc.2005,102(43):15545-15550.
[14]Edelman EJ, Guinney J, Chi JT, et al. Modeling cancer progression via pathway dependencies. PLoS Comput Biol.2008; 4(2):e28..
[15]Morris DS, Tomlins SA, Rhodes DR, et al. Integrating biomedical knowledge to model pathways of prostate cancer progression. Cell Cycle.2007; 6(10):1177-87.
[16]Sauter ER, Lininger J, Magklara A, et al. Association of kallikrein expression in nipple aspirate fluid with breast cancer risk. Int J Cancer.2004, 108(4):588-91.
[17]Tomlins SA, Rubin MA, Chinnaiyan AM. Integrative biology of prostate cancer progression. Annu Rev Pathol.2006;1:243-71.
[18]金冬雁,黎孟枫等译.分子克隆实验指导(第二版)[M].科学出版社,2000.
[19]Chetcuti A, Margan S, Mann S, et al. Identification of differentially expressed genes in organ-confined prostate cancer by gene expression array. Prostate 2001; 47:132-140.
[20]Bull JH, Ellison G, Patel A, et al. Identification of potential diagnostic markers of prostate cancer and prostatic intraepithelial neoplasia using cDNA microarray. Br J Cancer 2001; 84:1512-1519.
[21]Lessick M, Katz A. A genetics perspective on prostate cancer. Urol Nurs.2006; 26(6):454-60.
[22]Singh D, Febbo PG, Ross K, et al. Gene expression correlates of clinical prostate cancer behavior. Cancer Cell 2002; 1:203-209.
[23]Huppi K, Chandramouli GV. Molecular profiling of prostate cancer. Curr Urol Rep.2004 Feb;5(1):45-51.
[24]邵晨,朱峰,晏伟等.改良消减杂交方法克隆前列腺癌细胞凋亡相关基因.中华泌尿外科杂志.2001,22(8)：479-482.
[25]周利群,杨学贞,黄啸等.应用基因微矩阵芯片筛选前列腺癌的相关基因.中华泌尿外科杂志.2002,23(2)：72-75.
[26]Attard G, Ang JE, Olmos D, et al. Dissecting prostate carcinogenesis through ETS gene rearrangement studies:implications for anticancer drug development. J Clin Pathol.2008; 61(8):891-6.
[27]Tomlins S, Mehra R, Rhodes D, et al. Integrative molecular concept modeling of prostate cancer progression. Nat Genet.2007;39:41-51.
[28]Aerts JL, Gonzales MI, Topalian SL. Selection of appropriate control genes to assess expression of tumor antigens using real-time RT-PCR. Biotechniques. 2004; 36(1):84-6,88,90-1.
[29]Vandesompele J, De Paepe A, Speleman F. Elimination of primer-dimer artifacts and genomic coamplification using a two-step SYBR green I real-time RT-PCR. Anal Biochem.2002; 303(1):95-8.
[30]Jeong YJ, Choi HW, Shin HS, et al. Optimization of real time RT-PCR methods for the analysis of gene expression in mouse eggs and preimplantation embryos. Mol Reprod Dev.2005; 71(3):284-9.
[31]Bengtsson M, Karlsson HJ, Westman G, Kubista M. A new minor groove binding asymmetric cyanine reporter dye for real-time PCR. Nucleic Acids Res, 2003,31(8):e45.
[32]Richardson TD, Oesterling JE. Age-specific reference ranges for serum prostate-specific antigen.Urol Clin North Am.1997; 24(2):339-51.
[33]Moroy T, Grzeschiczek A, Petzold S, et al. Expression of a PIM-1 transgene accelerates lymphoproliferation and inhibits apoptosis in lpr/lpr mice. Proc Natl Acad Sci USA,1993,90(22):10743-10748.
[34]Wang ZP, Nandini, Matt W, et al. PIM-1 a serine/threonine kinase with a role in cell survival, proliferation, differentiation and tumorigenesis]. Vet Sci,2001, 2(3):167-169.
[35]Leverson JD, Koskinen PJ, Orrico FC, et al. PIM-1 kinase and p100 cooperate to enhance c-Myb activity. Mol Cell,1998 2(4):417-425.
[36]Thompson J, Peltola KJ, Koskinen PJ, et al. Attenuation of androgen receptor-dependent transcription by serine/threonine kinase PIM-1. Lab Invest, 2000,83(9):1301-1309.
[37]翁迈,周利群,王建伟,等.PIM-1蛋白激酶在前列腺癌组织中的表达.基础医学与临床,2005,25：503-506
[38]张彤,徐勇,张淑敏,等.PIM-1在前列腺癌组织中的表达及与血清PSA的关系.中国男科学杂志,2005,19：19-21.
[39]Alexander Valdman, Xiaolei Fang, See-Tong Pang, et al.PIM-1 expression in prostatic intraepithelial neoplasia and human prostate cancer [J]. Prostate, 2004,60:367-371.
[40]钟惟德,李俊玲,何慧婵,等.实时荧光定量TR-PCR检测良性前列腺增生与前列腺癌相关基因表达的临床意义.中华泌尿外科杂志,2005,26：615-618.
[41]Obiezu CV, Diamandis EP. Human tissue kallikrein gene family:applications in cancer. Cancer Lett,2005,224(1):1-22
[42]Magklara A, Scorias A, Lopen-OtinC, et al. Human Glandular Kallikrein in Breast Milk, Antiniotic Fluid and Breast Cyst Fluid. Clin Chem, 1999,45:1774-1780.
[43]Rittenhous HG, Finlay JA, Mikolaajczyk SD, et al. Human Kallikrein2(hK2)and Prostate Specific Antigen(SPA):How Closely Related, but District Kallikreins in the Prostate. Crit Rev Clin Lab Sci,1998,35:275-368.
[44]Becker C, Piironen T, Pettersson K, et al. Clinical value of human glandular kallikrein 2 and free and total prostate-specific antigen in serum from a population of men with prostate-specific antigen levels 3.0 ng/mL or greater. Urology,2000,55(5):694-9.
[45]So A, Goldenberg L, Gleave ME. Prostate specific antigen:an updated review. Can J Urol,2003,10(6):2040-50.
[46]曾浩,李虹,张秀辉,等.前列腺特异性膜抗原表达的临床意义.中华泌尿外科杂志,2003,6：392-394.
[47]Wilson CM, McPhaul MJ. A and B forms of the androgen re2ceptor are present in human genital skin fibroblasts. ProcNatl Acad Sci USA,1994,91(4):1234-1238.
[48]Brolin J,Skoog l,Ekman P.Immunohhistochemistry and biochemistyy in detection of androgen, progesterone,and estrogen receptors in benign and malignant human prostate tissue.Prostate,1992;20940:281-283
[49]Lu ML, Schneider MC, Zheng Y, et al. Caveolin21 interacts with androgen receptor. A positive modulator of androgen receptor mediated transactivation. J Biol Chem,2001,276:13442213451.
[50]Sweat SD.Pacelli A, Bergstralh E, Slezak J. Bostwick D Androgen receptor expression in prostatic intraepithelial neoplasia and cancer, J Urol,1999; 161(4);1229-1232.
[51]Ma XJ, Hilsenbeck SG, Wang W, et al. The HOXB13:IL17BR expression index is a prognostic factor in early-stage breast cancer. J Clin Oncol. 2006;24(28):4611-9.
[52]Ma XJ, Wang Z, Ryan PD, et al. A two-gene expression ratio predicts clinical outcome in breast cancer patients treated with tamoxifen.
[53]Reed CE, Graham A, Hoda RS, et al. A simple two-gene prognostic model for adenocarcinoma of the lung. J Thorac Cardiovasc Surg.2008;135(3):627-34.
[54]Wang X, Li X, Currie R.W, Willette RN, Barone FC, Feuerstein G.Z. Application of real-time polymerase chain reaction to quantitate induced expression of interleukin-lbeta mRNA in ischemic brain tolerance. J Neurosci Res.2000 Jan 15; 59(2):238-46.
[55]Diamandis EP, Yousef GM, Luo LY, Maqklara A, Obiezu CV. The new human kallikrein gene family:implications in carcinogenesis[J].Trends EndocrinolMetab,2000,11 (2):54-60.
[56]Yousef GM, Diamandis EP. The new human tissue kallikrein gene family: structure, function, and association to disease[J]. Endocr Revl2001,22 (2) 184-204.
[57]Diamandis EP, Yousef GM. Human tissue kallikreins:a family of new cancer biomarkers[J]. Clin Chem,2002, Aug;48(8):1198-205.
[58]Paliouras M, Borgono C, Diamandis EP. Human tissue kallikreins:The cancer biomarker family. Cancer Lett.2007 Apr 28;249(1):61-79.
[59]Lin B, Ferguson C, White JT, Wang S, Vessella R, True LD, Hood L, Nelson PS.Prostate-localized and Androgen-regulated Expression of the Membrane-bound Serine Protease TMPRSS2[J]. CANCER RESEARCH,1999, 59(17):4180-4184.
[60]Afar DE, Vivanco I, Hubert RS, Kuo J, Chen E, Saffran DC, Raitano AB, Jakobovits A. Catalytic cleavage of the androgen-regulated TMPRSS2 protease results in its secretion by prostate and prostate cancer epithelia. Cancer Res. 2001 Feb 15;61(4):1686-1692.
[61]Gan L, Lee I, Smith R, Argonza-Barrett R, Lei H, McCuaig J, Moss P, Paeper B, Wang K. Sequencing and expression analysis of the serine protease gene cluster located in chromosome 19q13 region[J]. Gene.2000 Oct 17;257(1):119-30.
[62]Scorilas A, Gregorakis AK. mRNA expression analysis of human kallikrein 11 (KLK11) may be useful in the discrimination of benign prostatic hyperplasia from prostate cancer after needle prostate biopsy[J]. Biol Chem.2006 Jun;387(6):789-793.
[63]Nakamura T, Stephan C, Scorilas A, Yousef GM, Jung K, Diamandis EP. Quantitative analysis of hippostasin/KLK11 gene expression in cancerous and noncancerous prostatic tissues[J]. Urology.2003 May;61(5):1042-1046.
[64]Morris GF, Mathews MB. Regulation of proliferating cell nuclear antigen during the cell cycle[J]. J Biol Chem,1989,264:13856.
[65]Brabo R,Macdonalc, bravo H. Existense of two populations of cyclin/ proliferating cell nuclear antigen during the cell cycle:association with DNA replication sites [J]. J Cell Biol,1987,105 (4):1549.
[66]Chapel F, Guettier C, Chastang C, Rached AA, Mathieu D, Tepper M, Beaugrand M, Trinchet JC. Needle biopsy of hepatocellular carcinoma: assessment of prognostic contribution of histologic parameters including proliferating cell nuclear antigen labeling and correlations with clinical outcomes. Group d'Etude et de Traitement du Carcinoma Hepatocellulaire[J]. Cancer.1996 Mar 1;77(5):864-71.
[67]董昌元,王玲,王贤明,易建华,姚启盛.前列腺癌组织中PCNA、MVD表达与彩超血流检测的研究[J].中国临床医学影像杂志,2007,18(1)：56-58.
[68]孙衍增,牛兆山.P53蛋白和增殖细胞核抗原在前列腺癌中的表达及意义[J].青岛大学医学院学报,2001,37(4)：309-311.
[69]郭琳琅.增殖细胞核抗原在前列腺疾病中的表达及意义[J].临床泌尿外科杂志,1997,12：302.
[70]Nemoto R, Kawamura H, Miyakawa I, Uchida K, Hattori K, Koiso K, Harada M.. Immunohistochemical detection of proliferating cell nuclear antigen (PCNA)/cyclin in human prostate adenocarcinoma [J]. J Urol,1993,149:165
[71]阎洪涛,龚百生,廖勇,杨红,陈照祥.前列腺癌p53和PCNA表达的相关性研究[J].四川医学,2005,26(4)：429-430.
[72]龚百生,阎洪涛,廖勇,杨红,陈照祥.前列腺癌PSA和PCNA表达的相关性研究[J].临床泌尿外科杂志,2006,21(3)：167-170.
[73]朱德茂,杨志,聂长庆.前列腺癌术前细针穿刺涂片的PCNA表达及意义[J].中国肿瘤临床与康复,2002,9(5)：26-27.
[74]Spires S E,Banks E R,Davey D D. Proliferating ell nuclear antigen in prostatic adenocarcinoma:correlation with established prognostic indicators [J]. Urology,1994,43 (5):660.
[75]Gerdes J, Schwab U, Lemke H, Stein H. Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation [J]. Int J Cancer,1983,31(1):13-20.
[76]Charpin C, Dicaire MJ, Barbeau B, Lavaut MN, Andonian C, Devictor B, Allasia C, Bonnier P, Mandeville R. Monoclonal 3C6F9 distribution in human breast carcinomas:image cytometry of immunocytochemical assays[J]. Med Oncol Tumor Pharmacother,1991,8(4):243-251.
[77]Halvorsen OJ, Haukaa S, Hoisaeter PA, Akslen LA.. Maximum Ki-67 staining in prostate cancer provides indepent prognostic information after radical prostatectomy [J]. Anticancer Res,2001,21 (6A):4071-4076.
[78]Munoz E, Gomez F, Paz JI, Casado I, Silva JM, Corcuera MT, Alonso MJ. Ki-67 immunolabeling in pre-malignant lesions and carcinoma of the prostate. Histologic correlation and prognostic evaluation[J]. Eur J Histochem,2003,47 (2):123-128.
[79]Claudio PP, Zamparelli A, Garcia FU, Claudio L, Ammirati G, Farina A, Bovicelli A, Russo G, Giordano GG, McGinnis DE, Giordano A, Cardi G. Expression of Cell-cycle-regulated Protein PRb2/P130, P107, P27-kipl, P53, mdm-2, and Ki-67(MIB-1) in prostatic gland adenocarcinoma[J]. Clin Cancer Res,2002,8(6):1808-1815.
[80]刘喜波,孟春琴.Ki-67和CK34PE12在前列腺癌鉴别诊断中的应用[J].肿瘤研究与临床,2005,17(3)：187-188.
[81]Bantis A, Giannopoulos A, Gonidi M, Liossi A, Aggelonidou E, Petrakakou E, Athanassiades P, Athanassiadou P. Expression of P120,Ki-67and PCNA as proliferation biomarkers in imprint smears of prostate carcinoma and their prognostic smears of prostate carcinoma and their prognostic value. Cytopathology.2004 Feb;15(1):25-31.
[82]8Scherer DC, Brockman JA, Chen Z, Maniatis T, Ballard DW. Signal-induced degradation of I kappa B alpha requires site-specific ubiquitination[J]. Proc Natl Acad Sci U S A.1995,92(24):11259-63.
[83]Johnson MI, Hamdy FC. Apoptosis regulating genes in prostate cancer[J]. Oncol Rep,1998,5(3):553-7.
[84]Karan D, Lin MF, Johansson SL, Batra SK. Current status of the molecular genetics of human prostatic adenocarcinomas[J]. Int J Cancer,2003,103(3): 285-93.
[85]Chen F, Castranova V, Shi X. New insights into the role of nuclear factor-B in cell growth regulation[J]. Am J Pathol,2001,159:387-97.
[86]Gilmore TD. The Rel/NF-B/I B signal transduction pathway and cancer[J]. Cancer Treat Res,2003,115:241-65.
[87]Pfitzenmaier J, Vessella R, Higano CS, Nnteboom JL, Wallace D Jr, Corey E. Elevation of cytokine levels in cachectic patients with prostate carcinoma[J]. Cancer,2003,97(5):1211-6.
[88]Shukla S, Gupta S. Suppression of constitutive and tumor necrosis factor alpha-induced nuclear factor (NF)-kappaB activation and induction of apoptosis by apigenin in human prostate carcinoma PC-3 cells:correlation with down-regulation of NF-kappaB-responsive genes[J]. Clin Cancer Res.2004,10(9): 3169-78.
[89]D. Horton, J.L. Goldstein and M.S. Brown, SREBPs:activators of the complete program of cholesterol and fatty acid synthesis in the liver[J]. J. Clin. Invest. 2002,109(9):1125-1131.
[90]Swinnen JV, Heemers H, van de Sande T, de Schrijver E, Brusselmans K, Heyns W, Verhoeven G. Androgens, lipogenesis and prostate cancer[J]. J Steroid Biochem Mol Biol.2004,92(4):273-9.
[91]Marmor MD, Skaria KB, Yarden, Y. Signal transduction and oncogenesis by ErbB/HER receptors[J]. Int J Radiat Oncol Biol Phys,2004,58(3):903-13.
[92]陈立勇,郭宁.HER2参与的基因表达调控[J].生物技术通讯,2006,3(17)：398-401.
[93]Galmozzi E, Casalini P, Iorio MV, Casati B, Olqiati C, Menard S. HER2 signaling enhances 5'-UTR-mediated translation of c-Myc mRNA[J]. J Cell Physiol,2004,200 (1):82-8.
[94]曾益新主编.肿瘤学[M].人民卫生出版社,2003.
[95]Livak KJ, SchmittgenTD. Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2-ΔΔCT Method. Methods.2001; 25:402-408.
[96]杨光华.肿瘤病理学[M].第五版.北京人民卫生出版社2000.107-121
[97]王建业.前列腺疾病与临床实践[M].北京出版社2002.229
[98]Yousef GM,Luol-Y, D iamandis E P.Indentification of novel human kallikrein-like genes on chromosome 19q13.3-19q13.4[J] Aticancer Res,1999,19: 2843-2852.
[99]Diamandis EP, Yousef GM. Human tissue kallikreins:a family of new cancer biomarkers[J].Clin Chem,2002,48:1198-1205.
[100]Myers SA, Clements JA. Kallikrein-4(KLK4), a new member of the human kallikrein gene family up-regulated by estrogen and progesterone in the human endometrial cancer cell line[J]. KLEJ Clin Endocrinol Metab, 2001,86:2323-2326.
[101]ChristinaV. Obiezu, Andreas Scorilas, Dionyssios Katsaros. Higher human kallikrein gene 4 expression indicates poor prognosis os ovarian cancer
patients[J]. Clinical cancer research,2001,7:2380-2386.
[102]董志伟.中国癌症研究进展——中国主要癌症的筛查及早诊早治[M].北京大学医学出版社,2004,12：252.
[103]Wang MC, Murphy GP, Chu TM. Purification of a human prostate specific antigen[J]. Invest Urol,1979:159-163.
[104]Stenner J, Holthaus K, Mackenzie SH, Crawford ED. The effect of ejaculation on prostate-specific antigen in a prostate cancer-screening population[J]. Urology,1998,51(3):455-459.
[105]张华,许叔祥.定量聚合酶链反应的研究进展与临床应用[J].中华检验医学杂志,2000,23(2)：120-121.
[106]Schweitzer B, Kingsmore S. Combining nucleic acid amplification and detection[J]. Current Opinions in Biotechnology,2001,12:21-27.
[107]Eis PS, Olson MC, Takova T, Curtis ML, Olson SM, Vener TI, Ip HS, Vedvik KL, Bartholomay CT, Allawi HT, Ma WP, Hall JG, Morin MD, Rushmore TH, Lyamichev VI, Kwiatkowski RW. An invasive cleavage assay for direct quantitation of specific RNAs[J]. Nature Biotechnology,2001,19:673-676.
[108]Klein D. Quantification using real-time PCR technology:applications and limitations[J]. TRENDS in Molecular Medicine,2002,8:257-259.
[109]Bonnet G, Tyagi S, Libchaber A, Kramer FR. Thermodynamic basis of the enhanced specificity of structured DNA probes[J]. PNAS,1999, 96:6171-6176.
[110]Gut M, Leutenegger CM, Huder JB, Pedersen NC, Lutz H.. One-tube fluorogenic reverse transcription-polymerase chain reaction for the quantitation of feline coronaviruses[J]. Journal of Virological Methods,1999, 77:37-46.
[111]Tyagi S, Kramer FR. Molecular beacons:probes that fluoresce upon hybridization[J]. Nature Biotechnology,1996,14:303-308.
[112]Taveau M, Stockholm D, Spencer M, Richard I. Taveau M, Stockholm D, Spencer M. Quantification of splice variants using molecular beacon or scorpion primers[J]. Anal Biochem.2002 Jun 15;305(2):227-35.
[113]Rickert AM, Borodina TA, Kuhn EJ, Lehrach H, Sperling S..Refinement of single-nucleotide polymorphism genotyping methods on human genomic DNA:amplifluor allele-specific polymerase chain reaction versus ligation detection reaction-TaqMan[J]. Analytical Biochemistry 2004;330:288-297.
[114]Saha BK, Tian B, Bucy RP. Quantitation of HIV-1 by real-time PCR with a unique fluorogenic probe[J]. J Virol Met 2001;93:33-42.
[115]施林祥,李东辉.实时荧光PCR研究新进展[J].世界华人消化杂志,2005,13(5)596-599.
[116]袁媛,陈强,陈思祗,刘中来.实时荧光定量PCR技术及其在生命科学领域中的应用(一)[J].海峡预防医学杂志,2006,12(4)：18-20.
[117]Pryor RJ, Wittwer CT. Real-time polymerase chain reaction and melting curve analysis[J]. Methods Mol Biol.2006;336:19-32.
[118]Bustin S. transcription absolute quantification of mRNA using real-time reverse
[119]polymerase chain reaction assays [J]. J Mol Endocrinol,2000,25:169-193.
[120]Sellars MJ, Vuocolo T, Leeton LA, Coman GJ, Degnan BM, Preston NP. Real-time RT-PCR quantification of Kuruma shrimp transcripts:A comparison of relative and absolute quantification procedures [J]. J Biotechnol.2007 Feb 9
[121]Leong DT, Gupta A, Bai HF, Wan G, Yoong LF, Too HP, Chew FT, Hutmacher DW. Absolute quantification of gene expression in biomaterials research using real-time PCR[J]. Biomaterials.2007 Jan;28(2):203-10.
[122]Bustin SA. Absolute quantification of mRNA using real-time reverse transcription polymerase chain reaction assays [J]. J Mol Endocrinol, 2000,25(2):169-193.
[123]Giulietti A, Overbergh L, Valckx D, Decallonne B, Bouillon R, Mathieu C. An overview of real-time quantitative PCR:applications to quantify cytokine gene expression[J]. Methods,2001,25(4):386-401.
[124]张燕,沈茜.一种快速构建cRNA标准曲线检测基因表达方法的建立[J].生物化学与生物物理进展,2003,30(3)：474-477.
[125]张弛宇,徐顺高,黄新祥.一种新颖简便的荧光实时RT-PCR相对定量方法的建立[J].生物化学与生物物理进展,2005,32(9)：883-888.
[126]Aliyu SH, Aliyu MH, Salihu HM, Parmar S, Jalal H, Curran MD. Rapid detection and quantitation of hepatitis B virus DNA by real-time PCR using a new fluorescent (FRET) detection system[J].J Clin Virol.2004 Jun;30(2):191-5.
[127]Singh M, Dicaire A, Wakil AE, Luscombe C, Sacks SL. Quantitation of hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) in the liver of HBV-infected patients by LightCycler real-time PCR[J]. J Virol Methods. 2004 Jun 15; 118(2):159-67.
[128]D.L.斯佩克特,R.D.戈德曼,L.A.莱因万德.细胞实验指南(上册)[M].科学出版社,2001.
[129]Donald S Coffey. Prostate cancer:an overview of increasing dilemma[J]. Cancer,1993,71:880-886.
[130]Maliner-Stratton M S, Klein R D,Udayakumar T S, Nagle RB, Bowden GT. Interleukin-1 beta-induced promatrilysin expression is mediated by NFkappaB-regulated synthesis of interleukin-6 in the prostate carcinoma cell line, LNCaP.Neoplasia.2001,3(6):509-20.
[131]Murphy GP. Models for prostate cancer[M]. New York:Liss; 1980:115-132.
[132]Kaighn ME, Narayan KS, Ohnuki Y, Lechner JF, Jones LW. Establishment and characterization of a human prostatic carcinoma cell line (PC-3)[J]. Invest. Urol.17:16-23,1979.
[133]Grossmann ME, Huang H, Tindall DJ. Androgen receptor signaling in androgen-refractory prostate cancer[J]. J Natl Cancer Inst,2001,93(22): 1687-1697.
[134]Feldman BJ, Feldman D. The development of androgen-independent prostate cancer[J]. Nat Rev Cancer,2001,1(1):34-45.
[135]A de la Taille, F Vacherot, L Salomon, C Drue, S Gil Diez de Medina, C Abbou, R Buttyan, D Chopin. Hormone-refractory prostate cancer:a multi-step and multi-event process[J]. Prostate Cancer Prostatic Dis, 2001,4(4):204-212.
[136]Zhao H, Kim Y, Wang P, Lapointe J, Tibshirani R, Pollack JR, Brooks JD. Genome-Wide Characterization of Gene Expression Variations and DNA Copy Number Changes in prostate Cancer Cell Lines. The Prostate 63:187-197 (2005).
[137]金冬雁,黎孟枫等译.分子克隆实验指导(第二版)[M].科学出版社,2000.
[138]Bengtsson M, Karlsson HJ, Westman G, Kubista M. A new minor groove binding asymmetric cyanine reporter dye for real-time PCR[J]. Nucleic Acids Res,2003,31 (8):e45.
[139]Espy MJ, Uhl JR, Sloan LM, Buckwalter SP, Jones MF, Vetter EA, Yao JD, Wengenack NL, Rosenblatt JE, Cockerill FR 3rd, Smith TF. Real-time PCR in clinical microbiology:applications for routine laboratory testing. Clin Microbiol Rev.2006 Jan; 19(1):165-256.
[140]Bustin SA. Absolute quantification of mRNA using real-time reverse transcription polymerase chain reaction assays[J]. Molecular Endocrinology, 2000,25:169.
[141]Wang X, Li X, Currie R.W, Willette RN, Barone FC, Feuerstein G.Z. Application of real-time polymerase chain reaction to quantitate induced expression of interleukin-lbeta mRNA in ischemic brain tolerance. J Neurosci Res.2000 Jan 15; 59(2):238-46.
[142]de Kok JB, Ruers TJ, van Muijen GN, van Bokhoven A, Willems HL, Swinkels DW. Real-time quantification of human telomerase reverse transcriptase mRNA in tumors and healthy tissues. Clin Chem.2000 Mar;46(3):313-8.
[143]Moody A, Sellers S, Bumstead N. Measuring infectious bursal disease virus RNA in blood by multiplex real-time quantitative RT-PCR[J]. Virol. Methods,2000,Mar; 85(1-2):55-64.
[144]钟惟德,李俊玲,何慧婵,江福能,刘文华,毕学成,彭志强,刘良式,魏鸿蔼.实时荧光定量RT-PCR检测良性前列腺增生与前列腺癌相关基因表 达的临床意义[J].中华泌尿外科杂志,2005,26(9)：615-618.
[145]Ostrander EA, Stanford JL. Genetics of prostate cancer:too many loci, too few genes. Am J Hum Genet,2000,Dec; 67(6):1367-1375.
[146]Diamandis EP, Yousef GM, Luo LY, Maqklara A, Obiezu CV. The new human kallikrein gene family:implications in carcinogenesis[J].Trends EndocrinolMetab,2000,11 (2):54-60.
[147]Yousef GM, Diamandis EP. The new human tissue kallikrein gene family: structure, function, and association to disease[J]. Endocr Revl2001,22 (2) 184-204.
[148]Diamandis EP, Yousef GM. Human tissue kallikreins:a family of new cancer biomarkers[J]. Clin Chem,2002, Aug;48(8):1198-205.
[149]Paliouras M, Borgono C, Diamandis EP. Human tissue kallikreins:The cancer biomarker family. Cancer Lett.2007 Apr 28;249(1):61-79.
[150]Lin B, Ferguson C, White JT, Wang S, Vessella R, True LD, Hood L, Nelson PS. Prostate-localized and Androgen-regulated Expression of the Membrane-bound Serine Protease TMPRSS2[J]. CANCER RESEARCH, 1999,59(17):4180-4184.
[151]Afar DE, Vivanco I, Hubert RS, Kuo J, Chen E, Saffran DC, Raitano AB, Jakobovits A. Catalytic cleavage of the androgen-regulated TMPRSS2 protease results in its secretion by prostate and prostate cancer epithelia. Cancer Res.2001 Feb 15;61(4):1686-1692.
[152]Gan L, Lee I, Smith R, Argonza-Barrett R, Lei H, McCuaig J, Moss P, Paeper B, Wang K. Sequencing and expression analysis of the serine protease gene cluster located in chromosome 19q13 region[J]. Gene.2000 Oct 17;257(1):119-30.
[153]Scorilas A, Gregorakis AK. mRNA expression analysis of human kallikrein 11 (KLK11) may be useful in the discrimination of benign prostatic hyperplasia from prostate cancer after needle prostate biopsy[J]. Biol Chem.2006 Jun;387(6):789-793.
[154]Nakamura T, Stephan C, Scorilas A, Yousef GM, Jung K, Diamandis EP. Quantitative analysis of hippostasin/KLK11 gene expression in cancerous and noncancerous prostatic tissues[J]. Urology.2003 May;61(5):1042-1046.
[155]Morris GF, Mathews MB. Regulation of proliferating cell nuclear antigen during the cell cycle[J]. J Biol Chem,1989,264:13856.
[156]Brabo R,Macdonalc, bravo H. Existense of two populations of cyclin/ proliferating cell nuclear antigen during the cell cycle:association with DNA replication sites [J]. J Cell Biol,1987,105 (4):1549.
[157]Chapel F, Guettier C, Chastang C, Rached AA, Mathieu D, Tepper M, Beaugrand M, Trinchet JC. Needle biopsy of hepatocellular carcinoma: assessment of prognostic contribution of histologic parameters including proliferating cell nuclear antigen labeling and correlations with clinical outcomes. Group d'Etude et de Traitement du Carcinoma Hepatocellulaire[J]. Cancer.1996 Mar 1;77(5):864-71.
[158]董昌元,王玲,王贤明,易建华,姚启盛.前列腺癌组织中PCNA、MVD表达与彩超血流检测的研究[J].中国临床医学影像杂志,2007,18(1)：56-58.
[159]孙衍增,牛兆山.P53蛋白和增殖细胞核抗原在前列腺癌中的表达及意义[J].青岛大学医学院学报,2001,37(4)：309-311.
[160]郭琳琅.增殖细胞核抗原在前列腺疾病中的表达及意义[J].临床泌尿外科杂志,1997,12：302.
[161]Nemoto R, Kawamura H, Miyakawa I, Uchida K, Hattori K, Koiso K, Harada M.. Immunohistochemical detection of proliferating cell nuclear antigen (PCNA)/cyclin in human prostate adenocarcinoma [J]. J Urol,1993,149:165
[162]阎洪涛,龚百生,廖勇,杨红,陈照祥.前列腺癌p53和PCNA表达的相关性研究[J].四川医学,2005,26(4)：429-430.
[163]龚百生,阎洪涛,廖勇,杨红,陈照祥.前列腺癌PSA和PCNA表达的相关性研究[J].临床泌尿外科杂志,2006,21(3)：167-170.
[164]朱德茂,杨志,聂长庆.前列腺癌术前细针穿刺涂片的PCNA表达及意义[J].中国肿瘤临床与康复,2002,9(5)：26-27.
[165]Spires S E,Banks E R,Davey D D. Proliferating ell nuclear antigen in prostatic adenocarcinoma:correlation with established prognostic indicators [J]. Urology,
[166]1994,43 (5):660.
[167]Gerdes J, Schwab U, Lemke H, Stein H. Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation [J]. Int J Cancer,1983,31(1):13-20.
[168]Charpin C, Dicaire MJ, Barbeau B, Lavaut MN, Andonian C, Devictor B, Allasia C, Bonnier P, Mandeville R. Monoclonal 3C6F9 distribution in human breast carcinomas:image cytometry of immunocytochemical assays[J]. Med Oncol Tumor Pharmacother,1991,8(4):243-251.
[169]Halvorsen OJ, Haukaa S, Hoisaeter PA, Akslen LA.. Maximum Ki-67 staining in prostate cancer provides indepent prognostic information after radical prostatectomy [J]. Anticancer Res,2001,21 (6A):4071-4076.
[170]Munoz E, Gomez F, Paz JI, Casado I, Silva JM, Corcuera MT, Alonso MJ. Ki-67 immunolabeling in pre-malignant lesions and carcinoma of the prostate. Histologic correlation and prognostic evaluation[J]. Eur J Histochem,2003,47 (2):123-128.
[171]Claudio PP, Zamparelli A, Garcia FU, Claudio L, Ammirati G, Farina A, Bovicelli A, Russo G, Giordano GG, McGinnis DE, Giordano A, Cardi G. Expression of Cell-cycle-regulated Protein PRb2/P130, P107, P27-kipl, P53, mdm-2, and Ki-67(MIB-1) in prostatic gland adenocarcinoma[J]. Clin Cancer Res,2002,8(6):1808-1815.
[172]刘喜波,孟春琴.Ki-67和CK34βE12在前列腺癌鉴别诊断中的应用[J].肿瘤研究与临床,2005,17(3)：187-188.
[173]Bantis A, Giannopoulos A, Gonidi M, Liossi A, Aggelonidou E, Petrakakou E, Athanassiades P, Athanassiadou P. Expression of P120,Ki-67and PCNA as proliferation biomarkers in imprint smears of prostate carcinoma and their prognostic smears of prostate carcinoma and their prognostic value. Cytopathology.2004 Feb;15(1):25-31.
[174]Scherer DC, Brockman JA, Chen Z, Maniatis T, Ballard DW. Signal-induced degradation of I kappa B alpha requires site-specific ubiquitination[J]. Proc Natl Acad Sci U S A.1995,92(24):11259-63.
[175]Johnson MI, Hamdy FC. Apoptosis regulating genes in prostate cancer[J]. Oncol Rep,1998,5(3):553-7.
[176]Karan D, Lin MF, Johansson SL, Batra SK. Current status of the molecular genetics of human prostatic adenocarcinomas[J]. Int J Cancer,2003,103(3): 285-93.
[177]Chen F, Castranova V, Shi X. New insights into the role of nuclear factor-κB in cell growth regulation[J]. Am J Pathol,2001,159:387-97.
[178]Gilmore TD. The Rel/NF-κB/IκB signal transduction pathway and cancer[J]. Cancer Treat Res,2003,115:241-65.
[179]Pfitzenmaier J, Vessella R, Higano CS, Nnteboom JL, Wallace D Jr, Corey E. Elevation of cytokine levels in cachectic patients with prostate carcinoma[J]. Cancer,2003,97(5):1211-6.
[180]Shukla S, Gupta S. Suppression of constitutive and tumor necrosis factor alpha-induced nuclear factor (NF)-kappaB activation and induction of apoptosis by apigenin in human prostate carcinoma PC-3 cells:correlation with down-regulation of NF-kappaB-responsive genes[J]. Clin Cancer Res. 2004,10(9):3169-78.
[181]D. Horton, J.L. Goldstein and M.S. Brown, SREBPs:activators of the complete program of cholesterol and fatty acid synthesis in the liver [J]. J. Clin. Invest.2002,109(9):1125-1131.
[182]Swinnen JV, Heemers H, van de Sande T, de Schrijver E, Brusselmans K, Heyns W, Verhoeven G. Androgens, lipogenesis and prostate cancer[J]. J Steroid Biochem
[183]Mol Biol.2004,92(4):273-9.
[184]Marmor MD, Skaria KB, Yarden, Y. Signal transduction and oncogenesis by ErbB/HER receptors[J]. Int J Radiat Oncol Biol Phys,2004,58(3):903-13.
[185]陈立勇,郭宁.HER2参与的基因表达调控[J].生物技术通 讯,2006,3(17)：398-401.
[186]Galmozzi E, Casalini P, Iorio MV, Casati B, Olqiati C, Menard S. HER2 signaling enhances 5'-UTR-mediated translation of c-Myc mRNA[J]. J Cell Physiol,2004,200 (1):82-8.
[187]曾益新主编.肿瘤学[M].人民卫生出版社,2003.