PTEN和C-myc在肺癌中的表达及意义
摘要
目的:探讨抑癌基因PTEN和癌基因C-myc在肺癌发生、发展中的作用及其相关性。
方法:采用免疫组织化学链霉菌抗生物素蛋白-过氧化酶法(S-P法),检测肺癌和肺正常组织切片中PTEN和C-myc蛋白表达。
结果:(1)C-myc蛋白在肺癌组织中的阳性表达率高于肺正常组织,具有显著性差异(P<0.01);而PTEN蛋白在肺癌组织中的阳性表达率显著低于肺正常组织(P<0.01)。(2)①PTEN和C-myc在不同病理类型、组织分化和有无淋巴结转移组之间的差异无显著性(P>0.05);②从中-高分化的肺癌组织到低分化肺癌组织C-myc表达有增强的趋势;相反,PTEN表达有降低的趋势;③C-myc在有转移组的肺癌组织中阳性表达率高于无转移组;相反,PTEN在有转移组的肺癌组织中阳性表达率低于无转移组,但差别都无显著意义(P?0.05)。(3)C-myc和PTEN在肺癌组织中的表达呈负相关(r=-0.4479,P< 0.01)。
结论:癌基因C-myc蛋白过度表达、抑癌基因PTEN蛋白的表达缺失在肺癌的发生、发展及转移过程中起促进作用,有望成为肺癌诊断和预后判断的标记物。
Objective : To investigate the correlation between the expressions of tumour suppressor gene PTEN and oncogene C-myc in lung carcinoma.
Methods : The expressions of PTEN and C-myc protein in normal lung tissue and lung carcinoma were observed by S-P immunohistochemical assay.
Results : (1)The expression of C-myc in the lung carcinoma tissues was significantly higher than that in the normal lung tissues(P<0.01); The positive expression of PTEN protein in the lung carcinoma tissues was significantly lower than that in the normal lung tissues(P<0.01).(2)①Difference was not found in groups of pathological types , differentiated degree and lymph node metastasis (P>0.05);②The expression of C-myc might increase concomitant with the progress from well group lung cancer to poor group lung cancer.On the contrary,a general decreasing tendency of PTEN seemed to accompany;③The positive rate of C-myc was higher in lymph node metastasis than that in non-lymph node metastasis,though the positive rate of PTEN was lower in lymph node metastasis than that in non-lymph node metastasis. (3) The level of C-myc protein expression was negatively correlated with PTEN expression(r=-0.4479,P< 0.01).
Conclusion: C-myc protein overexpression and the underexpression of PTEN was closely related to clinicopathological features in lung carcinoma,and could be used as a marker of tumour burden of lung carcinoma.
方法:采用免疫组织化学链霉菌抗生物素蛋白-过氧化酶法(S-P法),检测肺癌和肺正常组织切片中PTEN和C-myc蛋白表达。
结果:(1)C-myc蛋白在肺癌组织中的阳性表达率高于肺正常组织,具有显著性差异(P<0.01);而PTEN蛋白在肺癌组织中的阳性表达率显著低于肺正常组织(P<0.01)。(2)①PTEN和C-myc在不同病理类型、组织分化和有无淋巴结转移组之间的差异无显著性(P>0.05);②从中-高分化的肺癌组织到低分化肺癌组织C-myc表达有增强的趋势;相反,PTEN表达有降低的趋势;③C-myc在有转移组的肺癌组织中阳性表达率高于无转移组;相反,PTEN在有转移组的肺癌组织中阳性表达率低于无转移组,但差别都无显著意义(P?0.05)。(3)C-myc和PTEN在肺癌组织中的表达呈负相关(r=-0.4479,P< 0.01)。
结论:癌基因C-myc蛋白过度表达、抑癌基因PTEN蛋白的表达缺失在肺癌的发生、发展及转移过程中起促进作用,有望成为肺癌诊断和预后判断的标记物。
Objective : To investigate the correlation between the expressions of tumour suppressor gene PTEN and oncogene C-myc in lung carcinoma.
Methods : The expressions of PTEN and C-myc protein in normal lung tissue and lung carcinoma were observed by S-P immunohistochemical assay.
Results : (1)The expression of C-myc in the lung carcinoma tissues was significantly higher than that in the normal lung tissues(P<0.01); The positive expression of PTEN protein in the lung carcinoma tissues was significantly lower than that in the normal lung tissues(P<0.01).(2)①Difference was not found in groups of pathological types , differentiated degree and lymph node metastasis (P>0.05);②The expression of C-myc might increase concomitant with the progress from well group lung cancer to poor group lung cancer.On the contrary,a general decreasing tendency of PTEN seemed to accompany;③The positive rate of C-myc was higher in lymph node metastasis than that in non-lymph node metastasis,though the positive rate of PTEN was lower in lymph node metastasis than that in non-lymph node metastasis. (3) The level of C-myc protein expression was negatively correlated with PTEN expression(r=-0.4479,P< 0.01).
Conclusion: C-myc protein overexpression and the underexpression of PTEN was closely related to clinicopathological features in lung carcinoma,and could be used as a marker of tumour burden of lung carcinoma.
引文
[1] Pei L,Melmed S. Isolation and characterization of a pituitary tumor-transforming gene(PTTG)[J].Mol Endocrinol,1997,11(4):433-441
[2] Boxer LM,Dang CV.Translocations involving c-myc and c-myc function [J].Oncogene,2001,20(40):5595-5610
[3] 陈军.肿瘤相关基因.北京:北京医科大学出版社,1999,12:l25-l26
[4] Shibuya M,Yokota J,Ueyama Y.Amplication and exoression of a cellular oncogene(c-myc)in human gastric carcinoma.Mol Cell Biol,1985,5:414-418
[5] Askew DS,Ashmun RA,Simmons BC et a1.Constitutive c-myc expression in an IL-3-dependent myeloid cell line suppresses cell cycle arrest and acceleraters apoptosis.Oncogene, 1991,6:1915-1922
[6] Muller R,Bravo R,Burckhardt J,Curran T.Induction of c-fos gene and protein by growth factors precedes activation of C-myc.Nature,1984,312:716-720
[7] Liu LX,Jiang HC,Zhu AL.Gene expression profiles in liver cancer and normal liver tissues.World J Gastroenterol,2000,6(supp13):85
[8] 刘勇,路冬芝,潘伯荣.消化系肿瘤细胞增殖调控.新消化病学杂志,1997,5:532-533
[9] 姜泊,主编.细胞基础凋亡与临床.第1版.北京:人民军医出版社,1999,25-30
[10] Xu AG,Li SG,Liu JH,Gan AH.Function of apoptosis and expression of the proteins Bcl-2 P53 and C-myc in the development of gastric cancer.World J Gastroenterol 2001,7:403-406
[11] Li J,Yen C,Liaw D,et a1. PTEN,a putative protein tyrosine phosphatase gene mutated in human brain,breast and prostate cancer[J].Science,1997,275 (5308):1943-1947
[12] Li DM, Sun H. TEP1, encoded by a candidate tumor suppressor locus, is a novel protein tyrosine phosphatase regulated by transforming growth factor beta[J]. Cancer Res,1997,57(11):2124-2129
[13] Steck PA,Pershouse MA,Jasser SA,et a1.Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers[J].Nat Genet,1997,15(4):356-362
[14] Li J,Yen C,Liaw D,et a1.PTEN,a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer[J].Science,1997,275(5308):1943-1947
[15] Kohno T,Taoahashi M,Manda R,et al.Inactivtion of the PTEN/MMAC1/TEP1 gene in human lung cancers[J].Genes Chromosomes Cancer,1998,22:152-156
[16] 张 蕾,刘彤华,刘鸿瑞,等.PTEN/MMAC1/TEPT在肺癌中的丢失和失活[J].中华病理学杂志,2000,29(2):85-88
[17] Khaleghpour K,Li Y,Banville D,et a1.Involvement of the PI 3-kinase signaling pathway in progression of colon adenocarcinoma [J].Carcinogenesis,2004,25(2):241-248
[18] Jiang YA, Fan LF,Jiang CQ, et a1. Expression and significance of PTEN, hypoxia-inducible factor-1 alpha in colorectal adenoma and adenocarcinoma [J].World J Gastroenterol,2003,9 (3):491-494
[19] Sakurada A,Suzuki A,Sato M,et a1.Infrequent genetic alterations of the PTENPMMAC1 gene in Japanese patients with primary cancers of the breast,lung,pancreas,kidney,and ovary[J].Jpn J Cancer Res,1997,88(11):1025-1028
[20] Schmidt EV.The role of c-myc in regulation of translation initiation[J].Oncogene,2004,23(18):3217-3221
[21] Lilja JF,Wu D,Reynold RK, et a1.Growth suppression activity of the PTEN tumor suppressor gene in human endometrial cancer cells.Antican cer Res,2001 May-Jun,21(3B):1969-74
[22] Konopka B,Janiec-Jankowska A,Paszko Z, et a1. The coexistence of ERBB2, INT2, and CMYC oncogene amplifications and PTEN gene m utations in endometrial carcinoma[J].J Cancer Res Clin Oncol,2004,130(2):114-121
[23] Asano T,Yao Y,Zhu J,et a1.The PI3-kinase/Akt signaling pathway is activateddue to aberrant Pten expression and targets transcription factors NF-kappaB and c-Myc in pancreatic cancer cells[J].Oncogene,2004,23(53):8571-8580
[1] Li J,YenC,LiawD,et a1.PTEN,a putative protein tyrosine phosphatase gene mutated in human brain,breast,and prostate cancer[J].Science,1997,275(5308):1943-1947
[2]Lee JO,Yang H,Georgescu MM,et a1.Crystal structure of the PTEN tumor suppressor:implications for its phosphoinositide phosphatase activity and membrane association[J].Cell,1999,99(3):323-334
[3] Tolkacheva T,Chan AM.Inhibition of H-Ras transformation by the PTEN/MMACI/TEP1 tumor suppressor gene[J].Oncogene,2000,19(5):680-689
[4] 田新霞,吴浩强.新的肿瘤抑制基因的PTEN[J].中华病理学杂志,2000,6(29):455-457
[5] Stambolic V,Suzuki A,de la Pompa JL,et a1.Negative regulation of PKB/Akt dependent cellsurvival by the tumor suppressor PTEN[J].Cell,1998,95(1):29-39
[6] Tamura M,Gu J,Matsumoto K,et a1.Inhibition of cell migration,spreading,and focal adhesions by tumor suppressor PTEN[J].Science,1998,280:1614-1617
[7] Zundel W , Schindlcr C , et a1 . Loss of PTEN facilitates HIF-1-lmediated gene expression[J].Genes Dev,2000,15(4):319-326
[8] Di Cristofano A,Pesce B,Cordon-Cardo C,Pandolfi PP.PTEN is essential for embryonic development and tumor suppression[J].Nar Gener,1998,19(4):348-355
[9] Tian XX,Pang JC,To SS,et a1.Restoration of wild-type PTEN expression leads ro apoptesis,induces differentiation,and reduces telomerase activity in human glioma cells[J].J Neuropathol Exp Nurol,1999,58:472-479
[10] Koul D,Shen R,Garyali A,et a1. MMAC/PTEN tumor suppressor gene regulates vascular endothelial growth factor mediated angiogenesis in prostate cancer.Int J Oncol,2002,21:469-475
[11] Myers MP,Pass I,Batty IH ,et a1.The lipid phosphatase activity of PTEN is critical for its tumor supressor function.Proc Natl Acad Sci U S A ,1998,95:13513-13518
[12] Yu J,Ni M ,Xu J,et a1.Methylation profiling of twenty promoter-CpG islands of genes which may contribute to hepatocellular carcinogenesis.BMC Cancer,2002,2:29
[13] Frisk T ,Foukakis T ,Dwight T ,et a1.Silencing of the PTEN tumor-suppressor gene in anaplastic thyroid cancer. Genes Chromosomes Cancer,2002,35:74-80
[14] An Q,Liu Y,Gao Y,Huang J,et a1.Deletion of tumor suppressor genes in Chinese non-small cell lung cancer.Cancer Lett,2002,184:189-195
[15] Tamura M ,Gu J,Matsumoto K,et a1.Inhibition of cell migration,spreading,and focal adhesions by tumor suppressor PTEN.Science,1998,280:1614-1617
[16] Hosoya Y,Gemma A,Seike M,et a1.Alteration of the PTEN/MMAC1 gene locus in primary lung cancer with distant metastasis.Lung Cancer,1999,25:87-93
[17] Concharuk VN,del-Rosario A,et a1.Co-down regulation of PTEN,KAI-1,and nm23-H1 tumor/metastasis suppressor proteins in non-small cell lung cancer,2004,8(1):6-16.
[18]Olaussen KA,Soria JC.et a1.Loss of PTEN expression is not uncommon,but lacks prognostic value in stage I NSCLC[J],2003,23
[19] Bepler G,Sharma S,et a1.RRM1 and PTEN as prognostic parameters for overall and disease-free survival in patients with non-small cell lung cancer[J].2004,22(10):1878-1885
[20] Okomizo A,Tindall DJ,Drabkin H,et a1.PTEN/MMACl mutations identified in small cell,but not in non-small cell lung cancer[J].Oncogone,1998,17:475-479
[21] Forgacs E,Biesterveld EJ,Sekido Y,et a1.Mutation analysis of the PTEN/MMAC1 gene in lung cancer[J].Oncogene,1998,17:1557-l565
[22] 张蕾,刘彤华等.PTEN/MMACl/TEPT在肺癌中的丢失和失活[J].中华病理学杂志,2000,29(2):85-88
[23] Hong TM,Yang PC,Peck K,et a1.Profiling the downstream fenes of tumor suppressor PTEN in lung cancer cells by complementaty DNA microarray[J].AM J Respir Cell Mol Biol,2000,23:265-269
[24]Garte SJ.The c-myc oncogene in tumor progression[J].Crit Rev Oncog,1993,4(4):435-449
[25] Hann SR,Thompson CB,Eisenman RN,et a1.C-myc oncogene protein synthesis is independent of the cell cycle in human and avian cells[J].Nature,1985,314(6009):366
[26]Zajac-Kaye M .c-myc oncogene:a key component in cell cycle regulation its implication for lung cancer[J].Lung Cancer,2001,34(Suppl 2):S43
[27]吴建明,吴昌平.非小细胞肺癌中p65和C-myc的表达及意义[J].肿瘤防治研究,2003,30(5):359
[28]陈杰.端粒酶逆转录酶和c-myc基因在肺癌中表达的研究[J].临床内科杂志,2003,20(11):580
[29]李奇志,张胜名,毛永荣,等.非小细胞肺癌中C-myc蛋白表达及意义[J].Journal of Mathematical Medicine,2003,16(2):120
[30] Schmidt EV.The role of c-myc in regulation of translation initiation[J].Oncogene,2004,23(18):3217-3221
[31] Lilja JF,Wu D,Reynold RK, et a1.Growth suppression activity of the PTEN tumor suppressor gene in human endometrial cancer cells.Anti-cancer Res,2001 May_Jun,21 (3B):1969-1974
[32] Konopka B,Janiec-Jankowska A,Paszko Z, et a1. The coexistence of ERBB2, INT2, and C-MYC oncogene amplifications and PTEN gene mutations in endometrial carcinoma[J].JCancer Res Clin Oncol,2004,130(2):114-121
[33] Asano T,Yao Y,Zhu J,et a1.The PI3-kinase/Akt signaling pathway is activated due to aberrant Pten expression and targets transcription factors NF-kappaB and c-Myc in pancreatic cancer cells[J].Oncogene,2004,23(53):8571-8580
[34] 房学东,任辉,张研,等.结直肠癌组织抑癌基因PTEN和癌基因C-myc蛋白表达及其相关性[J].吉林大学学报,2007,33(3):570-573
[35]韦玮,吴晓玲,孙袁,等.C-myc、PTEN基因在子宫内膜癌中的表达及其相关性研究[J].中国妇幼保健,2005,20(15):1965-1967
[2] Boxer LM,Dang CV.Translocations involving c-myc and c-myc function [J].Oncogene,2001,20(40):5595-5610
[3] 陈军.肿瘤相关基因.北京:北京医科大学出版社,1999,12:l25-l26
[4] Shibuya M,Yokota J,Ueyama Y.Amplication and exoression of a cellular oncogene(c-myc)in human gastric carcinoma.Mol Cell Biol,1985,5:414-418
[5] Askew DS,Ashmun RA,Simmons BC et a1.Constitutive c-myc expression in an IL-3-dependent myeloid cell line suppresses cell cycle arrest and acceleraters apoptosis.Oncogene, 1991,6:1915-1922
[6] Muller R,Bravo R,Burckhardt J,Curran T.Induction of c-fos gene and protein by growth factors precedes activation of C-myc.Nature,1984,312:716-720
[7] Liu LX,Jiang HC,Zhu AL.Gene expression profiles in liver cancer and normal liver tissues.World J Gastroenterol,2000,6(supp13):85
[8] 刘勇,路冬芝,潘伯荣.消化系肿瘤细胞增殖调控.新消化病学杂志,1997,5:532-533
[9] 姜泊,主编.细胞基础凋亡与临床.第1版.北京:人民军医出版社,1999,25-30
[10] Xu AG,Li SG,Liu JH,Gan AH.Function of apoptosis and expression of the proteins Bcl-2 P53 and C-myc in the development of gastric cancer.World J Gastroenterol 2001,7:403-406
[11] Li J,Yen C,Liaw D,et a1. PTEN,a putative protein tyrosine phosphatase gene mutated in human brain,breast and prostate cancer[J].Science,1997,275 (5308):1943-1947
[12] Li DM, Sun H. TEP1, encoded by a candidate tumor suppressor locus, is a novel protein tyrosine phosphatase regulated by transforming growth factor beta[J]. Cancer Res,1997,57(11):2124-2129
[13] Steck PA,Pershouse MA,Jasser SA,et a1.Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers[J].Nat Genet,1997,15(4):356-362
[14] Li J,Yen C,Liaw D,et a1.PTEN,a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer[J].Science,1997,275(5308):1943-1947
[15] Kohno T,Taoahashi M,Manda R,et al.Inactivtion of the PTEN/MMAC1/TEP1 gene in human lung cancers[J].Genes Chromosomes Cancer,1998,22:152-156
[16] 张 蕾,刘彤华,刘鸿瑞,等.PTEN/MMAC1/TEPT在肺癌中的丢失和失活[J].中华病理学杂志,2000,29(2):85-88
[17] Khaleghpour K,Li Y,Banville D,et a1.Involvement of the PI 3-kinase signaling pathway in progression of colon adenocarcinoma [J].Carcinogenesis,2004,25(2):241-248
[18] Jiang YA, Fan LF,Jiang CQ, et a1. Expression and significance of PTEN, hypoxia-inducible factor-1 alpha in colorectal adenoma and adenocarcinoma [J].World J Gastroenterol,2003,9 (3):491-494
[19] Sakurada A,Suzuki A,Sato M,et a1.Infrequent genetic alterations of the PTENPMMAC1 gene in Japanese patients with primary cancers of the breast,lung,pancreas,kidney,and ovary[J].Jpn J Cancer Res,1997,88(11):1025-1028
[20] Schmidt EV.The role of c-myc in regulation of translation initiation[J].Oncogene,2004,23(18):3217-3221
[21] Lilja JF,Wu D,Reynold RK, et a1.Growth suppression activity of the PTEN tumor suppressor gene in human endometrial cancer cells.Antican cer Res,2001 May-Jun,21(3B):1969-74
[22] Konopka B,Janiec-Jankowska A,Paszko Z, et a1. The coexistence of ERBB2, INT2, and CMYC oncogene amplifications and PTEN gene m utations in endometrial carcinoma[J].J Cancer Res Clin Oncol,2004,130(2):114-121
[23] Asano T,Yao Y,Zhu J,et a1.The PI3-kinase/Akt signaling pathway is activateddue to aberrant Pten expression and targets transcription factors NF-kappaB and c-Myc in pancreatic cancer cells[J].Oncogene,2004,23(53):8571-8580
[1] Li J,YenC,LiawD,et a1.PTEN,a putative protein tyrosine phosphatase gene mutated in human brain,breast,and prostate cancer[J].Science,1997,275(5308):1943-1947
[2]Lee JO,Yang H,Georgescu MM,et a1.Crystal structure of the PTEN tumor suppressor:implications for its phosphoinositide phosphatase activity and membrane association[J].Cell,1999,99(3):323-334
[3] Tolkacheva T,Chan AM.Inhibition of H-Ras transformation by the PTEN/MMACI/TEP1 tumor suppressor gene[J].Oncogene,2000,19(5):680-689
[4] 田新霞,吴浩强.新的肿瘤抑制基因的PTEN[J].中华病理学杂志,2000,6(29):455-457
[5] Stambolic V,Suzuki A,de la Pompa JL,et a1.Negative regulation of PKB/Akt dependent cellsurvival by the tumor suppressor PTEN[J].Cell,1998,95(1):29-39
[6] Tamura M,Gu J,Matsumoto K,et a1.Inhibition of cell migration,spreading,and focal adhesions by tumor suppressor PTEN[J].Science,1998,280:1614-1617
[7] Zundel W , Schindlcr C , et a1 . Loss of PTEN facilitates HIF-1-lmediated gene expression[J].Genes Dev,2000,15(4):319-326
[8] Di Cristofano A,Pesce B,Cordon-Cardo C,Pandolfi PP.PTEN is essential for embryonic development and tumor suppression[J].Nar Gener,1998,19(4):348-355
[9] Tian XX,Pang JC,To SS,et a1.Restoration of wild-type PTEN expression leads ro apoptesis,induces differentiation,and reduces telomerase activity in human glioma cells[J].J Neuropathol Exp Nurol,1999,58:472-479
[10] Koul D,Shen R,Garyali A,et a1. MMAC/PTEN tumor suppressor gene regulates vascular endothelial growth factor mediated angiogenesis in prostate cancer.Int J Oncol,2002,21:469-475
[11] Myers MP,Pass I,Batty IH ,et a1.The lipid phosphatase activity of PTEN is critical for its tumor supressor function.Proc Natl Acad Sci U S A ,1998,95:13513-13518
[12] Yu J,Ni M ,Xu J,et a1.Methylation profiling of twenty promoter-CpG islands of genes which may contribute to hepatocellular carcinogenesis.BMC Cancer,2002,2:29
[13] Frisk T ,Foukakis T ,Dwight T ,et a1.Silencing of the PTEN tumor-suppressor gene in anaplastic thyroid cancer. Genes Chromosomes Cancer,2002,35:74-80
[14] An Q,Liu Y,Gao Y,Huang J,et a1.Deletion of tumor suppressor genes in Chinese non-small cell lung cancer.Cancer Lett,2002,184:189-195
[15] Tamura M ,Gu J,Matsumoto K,et a1.Inhibition of cell migration,spreading,and focal adhesions by tumor suppressor PTEN.Science,1998,280:1614-1617
[16] Hosoya Y,Gemma A,Seike M,et a1.Alteration of the PTEN/MMAC1 gene locus in primary lung cancer with distant metastasis.Lung Cancer,1999,25:87-93
[17] Concharuk VN,del-Rosario A,et a1.Co-down regulation of PTEN,KAI-1,and nm23-H1 tumor/metastasis suppressor proteins in non-small cell lung cancer,2004,8(1):6-16.
[18]Olaussen KA,Soria JC.et a1.Loss of PTEN expression is not uncommon,but lacks prognostic value in stage I NSCLC[J],2003,23
[19] Bepler G,Sharma S,et a1.RRM1 and PTEN as prognostic parameters for overall and disease-free survival in patients with non-small cell lung cancer[J].2004,22(10):1878-1885
[20] Okomizo A,Tindall DJ,Drabkin H,et a1.PTEN/MMACl mutations identified in small cell,but not in non-small cell lung cancer[J].Oncogone,1998,17:475-479
[21] Forgacs E,Biesterveld EJ,Sekido Y,et a1.Mutation analysis of the PTEN/MMAC1 gene in lung cancer[J].Oncogene,1998,17:1557-l565
[22] 张蕾,刘彤华等.PTEN/MMACl/TEPT在肺癌中的丢失和失活[J].中华病理学杂志,2000,29(2):85-88
[23] Hong TM,Yang PC,Peck K,et a1.Profiling the downstream fenes of tumor suppressor PTEN in lung cancer cells by complementaty DNA microarray[J].AM J Respir Cell Mol Biol,2000,23:265-269
[24]Garte SJ.The c-myc oncogene in tumor progression[J].Crit Rev Oncog,1993,4(4):435-449
[25] Hann SR,Thompson CB,Eisenman RN,et a1.C-myc oncogene protein synthesis is independent of the cell cycle in human and avian cells[J].Nature,1985,314(6009):366
[26]Zajac-Kaye M .c-myc oncogene:a key component in cell cycle regulation its implication for lung cancer[J].Lung Cancer,2001,34(Suppl 2):S43
[27]吴建明,吴昌平.非小细胞肺癌中p65和C-myc的表达及意义[J].肿瘤防治研究,2003,30(5):359
[28]陈杰.端粒酶逆转录酶和c-myc基因在肺癌中表达的研究[J].临床内科杂志,2003,20(11):580
[29]李奇志,张胜名,毛永荣,等.非小细胞肺癌中C-myc蛋白表达及意义[J].Journal of Mathematical Medicine,2003,16(2):120
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