摘要
目的:研究宫颈炎组织和宫颈癌组织中MHC-Ⅰ类抗原呈递相关蛋白(TAP_1、TAP_2、β2-MG、HSP70)的表达在维吾尔族和汉族妇女中的关系。初步探讨维吾尔族宫颈癌发病及发展过程中MHC-Ⅰ类抗原呈递相关蛋白TAP_1、TAP_2、β2-MG和HSP70在抗原呈递过程中的作用及影响因素。方法:应用免疫组织化学方法和聚合酶链反应(PCR)技术检测87例宫颈炎组织(维吾尔族36例,汉族51例)以及142例宫颈癌组织(维吾尔族99例,汉族43例)中HPV抗原呈递相关蛋白TAP_1、TAP_2、β2-MG和HSP70的表达和HPV16的感染情况。结果:TAP1、TAP2和β2-MG在宫颈癌组织中阳性表达率(51.61%、60.0%、61.42%),均低于宫颈炎组织(78.20%、94.81%、96.00%),(P<0.05)。
在宫颈癌组织中,汉族TAP1、TAP2和β2-MG阳性率分别为33.33%、42.11%和78.95%,维吾尔族TAP1、TAP2和β2-MG阳性率分别为59.09%、67.82%和53.93%。两组相比差异具有统计学意义(P<0.05)。
在宫颈炎组织中,汉族TAP1、β2-MG阳性率分别为70.21%和93.48%,维吾尔族TAP1、β2-MG阳性率分别为90.32%和100%。两组相比差异具有统计学意义(P<0.05)。
β2-MG与维吾尔族宫颈癌HPV16关系为正相关(r=0.216,P<0.05)。
汉族宫颈癌组织中,TAP2与β2-MG间存在正相关(r=0.331,P<0.05)。
维吾尔族宫颈癌组织中,TAP1与β2-MG之间、TAP1与HSP70之间存在正相关(r=0.351,P<0.05;r=0.224,P<0.05)。
结论:宫颈癌组织中TAP1、TAP2和β2-MG的表达量下降,且在维吾尔族和汉族间相关性表达呈现差异。提示不同蛋白在不同民族间宫颈癌的辅助诊断方面可能存在不一致。
Objective:study on the expression of MHC class I antigen presentation associated proteins TAP1, TAP2,HSP70,andβ2-MG in cervical cancer lesions and its correlation with HPV16 infection in cervical cancer patients of Uighur and Han women..Methods:We applied S-P Immunohistochemistry and PCR to detect the expression of proteins TAP1,TAP2,HSP70,β2-MG and infection of HPV16 respectively in 87 cervicitis tissues from 51 Han and 36 Uighur,women and 142 cervical cancer lesions from 43 Han and 99 Uighur women.Results:The expression rates of TAP1、TAP2、β2-MG in cervical cancer tissues from both Han and Uighur women(51.61%,60.0%, 61.42%,respectively) were significantly reduced when compared to that(78.20%,94.81%,.96.00%, respectively,and p<0.05) in cervicitis tissues from both ethnic groups.Among the cervical cancer tissues,the expression rate of TAP1、TAP2、β2-MG of Han women were 33.33%,42.11%,and 78.95%respectively,whereas the extression rate for these proteins of Uighur women were 59.09%, 67.82%,and 53.93%respectively,and the differences were significant between Han and Uighur women(p<0.05).In cervicitis tissues,the expression rate of TAP1 andβ2-MG were significantly different(p<0.05) between Han and Uighur women,that were 70.21%and 93.48%in former,and 90.32%and 100%in latter respectively.The expression rate ofβ2-MG in cervical cancer lesions was positively correlated with infection of HPV16 in Uighur women(r=0.216,p<0.05).There was positive correlation in expression ofβ2-MG and TAP2 in cervical cancers of Han women(r=0.331, p<0.05),and there were also positive correlations between expression ofβ2-MG and TAP1 and TAP1 and HSP70 in cervical cancers of Uighur women(r=0.351,p<0.05 and r=0.224,p<0.05, respectively).Conclusion:The expression of TAP1,TAP2 andβ2-MG in the cervical cancer lesions was reduced compared to the cervicitis tissues,and there were conelation differences in expression of these proteins between Han and Uighur women.This suggested possible discrepancies between different ethnic groups when considering the diagnostic significance of these protein expressions in cervical cancer lesions.
引文
[1]李冰,梁建荣,张慧敏,等.宫颈癌、卵巢癌与HLA的相关性[J].中国优生与遗传杂志,2005.3.25:13(3):63-64
[2]马正海,张富春,梅新娣,等.新疆维吾尔妇女宫颈癌组织中HPV16型E6基因突变分析[J].癌症,2004,23(9):1016-1020
[3]David R,Johson.Differential expression of human major histocompatibility class 1loci:HLA-A,-B,and-C[J].Hum.Immunol,2000,61:389
[4]ZUR HAUSEN H,de VILLIERS E M,GISSMANL.Papillomavirus infection and human genital cancer[J].Gynecol Oncol.1981,12:121-128
[5]谭毅,李淑玲,谢平.高危型人乳头瘤病毒联合细胞学检测原发和复发重度宫颈上皮内瘤变[J].实用医学杂志.2006,22(6):672-673
[6]Mclachlin C M.Human papillomavirus in cervical neoplasia:role,risk factors and Impllications[J].Clin Lab Med,2000,20(2):257
[7]廖彩森.宫颈癌流行病学及病因学研究进展[J].实用妇产科杂志.1994,10(5):229-231
[8]FR ISCH M,GOODMAN M T.Human pap illomavirus2associated carcinomas in Hawaii and the mainland U.S[J].Cancer.2000,88(6):1464-1469
[9]古扎丽努尔.阿不力孜,彭芝兰,王和,等.HPV各亚型在川西北汉族及南疆维吾尔族妇女宫颈癌组织中的差异表达[J].中华微生物及免疫学杂志.2004,24(5):408
[10]BOSCH F X,MANOSMM,MUNOZ N,et al.Prevalence of hu2man pap illomavirus in cervical cancer;a worldwide perspective.International biological study on cervical cancer[J].J National Cancer Insti.1995,87(11):796-2802
[11]吉.七年制妇产科学[M].北京.人民卫生出版社.2002
[12]于秀梅,姚庆英.宫颈亚临床HPV感染及性伴侣尿、精液与HPVl6-18型的关系[J].实用妇产科杂志.1998,14
[13]Karin ML,Szbing P,Association of human papillimavinus infection with carcinomal of the cervix and its precursor lesion:theoretical and practical implications Virchows Arch,2000,437-227
[14]Ferrera A,Velema J P,Figueroa M,et al.Human papillomavirus infection,cervical dysplasia and inbasive cervical cancer in Honduras:a case-control study[J].Int J Cancer,1999,82(6):799-803
[15]De Villiers EM,Gunst K,Stein H,et al.Esophageal squamous cell cancer in patients with head and neck cancer:prevalence of human pap illomavirusDNA sequences[J].Int J Cancer,2004,109(2):253
[16]CL IFFORD GM,SMITH J S,PLUMMER M,et al.Human pap il2 lomavirus types in invasive cervical cancerworldwide:a meta2anal2 ysis[J].Br J Cancer.2003,13,88(1):63-73
[17]关婷,张志文,谢燕芳等.人乳头瘤病毒基因型与宫颈上皮内瘤样病变的关系[J].重庆医学.2004,33(8):11 51-1152
[18]刘克洲,陈智 主编.人类病毒性疾病[M].北京:人民卫生出版社.2002,148
[19]Senior K,Cervical cancer research focuses on the HPV E7 gene[J].Lancet.2002,3(10):585
[20]于秀梅,姚庆英.宫颈亚临床HPV感染及性伴侣尿、精液与HPV16-18型的关系[J].实用妇产科杂志.1998,14(4):197-198
[21]闵洁,林美华.人巨细胞病毒感染与宫颈癌关系的研究[J].同济医科大学学报.2000,29:249
[22]李宝康.病毒感染与宫颈癌的相关性研究进展[J].重庆医学.2007,36(5):476-477
[23]Ritz U,Momburg F,Pilch H,Huber C,et al.Deficient expression of components of the MHC class I antigen processing machinery in human cervical carcinoma[J].Int J Oncol,2001,19:1211-1220
[24]Dovhey S E,Ghosh N S,Wrighe K L.Loss of interferon-gamma inducibility of TAP1and LMP2 in a renal cell carcinoma cell line[J].Cancer Res,2006,60:5789-5796
[25]Le Y S,Kim T E,Kim B K,et al.Alterations of HLA class Ⅰ and class Ⅱ antigen processing in borderline invasive and metastaic ovarian cancers[J].Exp Mol Med,2002,34:18-22
[26]Karin Biedermann.et al.Comparison of Real-Time PCR Signal-Amplified In Situ Hybridization and Conventional PCR for Detection and Quantification of Human Papillomavirus in Archival CervicalCancer Tissue[J].JOURANL OF CLINICAL MICROBIOLOGY,Aug.2004,p.3758-3765
[27]吴涓涓.分子伴侣与MHC分子[M].国家医学免疫学分册.2004,27(6):358-361
[28]W and FQ,Xi HK,Liu BB.Polymorphism of transporter associated with antigen processing TAP in a Shanghai population Chin[J].J Microbiol Immunol 1997,17(4):288-290
[29]Seliger B,Atkins D,Bock M,et al.Characterization of huMan lymphocyte antigen classⅠ antigen processingmachinery Defects in renal cell carcinoma lesions with special emphasis on transporter-associated with antigen-processing down regulation [J].Clin Cancer Res,2003,9(5):1721-1727.
[30]Zhu K,Wang J,Zhu J,et al.p53 induces TAP1 and enHances the transport of MHC class Ⅰ peptides[J].Oncogene.1999,18(54):7740-7747.
[31]Bobbie S.Gostout,M.D.et al.TAP1,TAP2,and HLA-DR2 alleles are predictors of cervical cancer risk[J].Gynecologic Ontology 88.2003:326-332
[32]Yang T,McNally BA,Ferrone S,et al.Asingle nucleotide Deletion leads to rapid degradation of TAP1 mRNA in amela2 cell line[J].J Biol Chem,2003,278(17):15291-15296.
[33]Cresswell AC,Sisley K,et.al.Reduced expression of TAP-1 and TAP-2 in posterior uveal melanoma is associated with progression to metastatic disease[J].Me lanoma Res.2001,Jun:11(3):275-81
[34]F.V.Cromme,J.Airey et al.Loss of Transporter,Encoded by the TAP-1 Gene,Is Highly Correlated with Loss of HLA Expression in Cervical Carcinomas[J].Exp.Med.The Rockefeller University Press.Volume 179 January 1994,335-340
[35]Menoret A,Partry Y,Burg C,et al.Co-segergation of tumor immunogenicity with expression of inducible but not constitutive HSP70 in rat colon carcinomas[J].J Immunol,1995,141(4):1340-1346
[36]Vitale M,Rezzani Rita,Rodella Luigi,et al[J].Cancer Res,1998,58(4):737-742
[37]Kozlowsk i S,Takeshita T,Boehncke WH,et al Excess beta 2-microglobulin promoting functional peptide association with purified soluble class Ⅰ MHC molecules[J]Nature,1991,349(6304):74-77
[38]Otten GR,Bikoff E,Ribaudo RK,et al Peptide and beta 2-microglobulin regulation of cell surface MHC class Ⅰ conformation and expression[J]J Immunol,1992,148:3723-3732
[39]Shields MJ,Assefi N,Hodgson W,et al Characterization of the interactions between MHC class Ⅰ subunits a systematic approach for the engineering of higher affinity variants of beta 2-microglobulin[J]J Immunol,1998,160:2297-2307
[40]Shields MJ,Kubota R,Hodgson W,et al The effect of human beta 2-microglobulin on major histocom patibility complex Ⅰ peptide loading and the engineering of a high affinity variant Implications for peptide-based vaccines[J]J Biol Chem,1998,273:28010-28018
[41]王征.肝硬化患者血、尿B2-微球蛋白检测意义[J].张家口医学院学报.2002,19(5):34
[42]王景萍,邵国庆.肝癌患者B2-微球蛋白检测意义探讨[J].中原医刊.2007,34(10):92
[43]苏丽芳.肿瘤病人血清B2-微球蛋白的测定及其临床意义[J].广州医药.1997,2(2):51
[44]王林.β2-微球蛋白在小儿疾病诊治中的研究进展[J].临床儿科杂志.2005,23(12):897-898
[45]张民军,叶伟民,陆慧琦,等.血、尿B2-微球蛋白在恶性实体瘤诊断中的价值[J].上海医学检验杂志.2001,16(3):169
[46]郑有文,姚立新,吕文臣,等.CA50、CEA、AFP、B2-M联合检测对提高消化道恶性肿瘤诊断率的价值探讨[J].河北医学.1999,5(10):7-9
[47]Sarma DP,Olivier M,et al.Beta-2-microglobulin an a marker of malignant epithelial tumors of the skin[J].Surg Oncol.1985,May;29(1):61-5
[48]Tesleni-Balafouta S,Balafoutas AC.Loss of beta 2 microglobulin from the surface of "dysplastic"and malignant epithelial cells of the uterine cervix[J].Zentralbl Gynakol.1989;111(11):744-8
[49]Petersen BL,Petersen CL.et al.Expression of beta 2-microglobulin by premalignant epithelium[J].APMIS.1993 Jul;101(7):529-36
[50]Cabrera CM,Nieto A.et al.The low rate of HLA class Ⅰ molecules on the human embryonic stem cell line HS293 is associated with the APM components'expression level[J].Cell Biol Int.2007 Sep;31(9):1072-8.
[51]武焕玲,邹雄等.胃癌患者HLA-Ⅰ,B7-1,β2m的表达[J].中国实验诊断学.2004,8(1):49-52
[52]Stebbing J,Gazzard B,Portsmouth S,et al.Disease-ssociated dendritic cells respond to disease-pecific antigens through the common heat shock protein receptor[J].Blood,2003,102(5):1806-1814
[53]Florin L,Becker K A,Sapp C,et al.Nuclear translocation of papillomavirus minor capsid protein L2 requires HSP90[J].J Virol,78(11):5546-5553
[54]K M KK,JANE TJ,KM JR Hsp70 and ER expression in cervical intraepithelial neoplasia and cervical cancer[J].Jkorean Sci 1998,13(4):383
[55]HELLMAN K,ALAIYA AA,SCHEDVNS K,et al Protein expression pattems in primary carcinoma of the vagina[J].Br J Cancer 2004,91(2):319-326
[56]Wang XP,Qiu FR,Liu GZ,et al Correlation between clinicopathology and expression of heat shock protein70 and glucose-regulated protein94 in human colonic adenocarcinoma[J].World J Gastroenterol,2005,11(70:1056-1059
[57]Lebret T,W atson RW,Molinie V.Heat shock proteins HSP27,HSP60,HSP70 and hsp90:expression in lbadder carcinomal Cancer[J].2003,98(5):970-977
[58]VanmuylderN,Evrard L,Daelemans P.Expression of heat shock proteins in salivary gland tumors Immunohistochemical studay of HSP27,HSP70,HSP90,HSP110:apropos of 50 cases[J].Ann Pathal,2000,20(3):190-195
[59]Kim KK,Jang TJ,Kim JT.HSP70 and ER expression in cervical intraepithelial neoplasia and cervical cancer[J].J Korean Med Sci,1998,13(4):383-388
[60]wei yq,zhao x,kariyay,et al.inhibition of proliferation and induction of apoptosis by abrogation of heat-shock protein(hsp70)expression in tumor cell.cancer immunol immunother,1995,40:73-78
[61]Tjalma WA,Weyler JJ,Bogers JJ,et al.The importance of biological factors (bcl-2,bax,p53,PCNA,MI,HPV and angiogenesis)in invasive cervical cancer[J].Eur J Obstet Gynecol Reprod Biod,2001,97(2):223-230
[62]陈向敏,夏克栋等.热休克蛋白70,p53,Bcl-2在宫颈癌组织中的表达及相关性研究[J].中国现代医学杂志.2005,15(2):253-255
[63]李达君,袁君,等.NMP238,HSP70在宫颈鳞癌中的表达及意义[J].中国医学工程.2007,15(4):320-326
[64]Yang Q,Sakurai T,Yoshimura G,et al Prognostic value of Bcl-2 in invasive breast cancer receiving chemotherapy and endocring therapy[J].Oncol Rep,2003,10(1):121-125
[65]Eur J.Long-term prognostic significance of HSP70 C-myc and HLA DR expression in patients with malignant melanoma[J].Eur J Surg Oncol,2001,27(1):88-93
[66]GUO YH,TIAN XY,MI JQ,et al Expression and significance of HSP70 and Bcl-2 in cervical squanous cell cancer[J].J Shandong Medical Joumal.2006,46(24):11-12.Chinese
[67]郭云鸿,田晓予,等.热休克蛋白70和热休克蛋白27在宫颈鳞癌中的表达及其意义[J].中原医刊.2006,33(24):4-6
[68]陈向敏,夏克栋,等.HSP70、P53、Bcl-2在宫颈癌组织中的表达及其与人乳头瘤病毒感染的关系[J].温州医学院学报.2004,34(4):288-289
[69]Carvalho MG,Foumier MV.Effect of heat shoed on gene expression of aedes albopictus cell infected with mayaro virus[J].Res Virol,1991,142:25
[70]Jindal S,Young PA,Vaccinia virus infetion induces a stress response that leads to association of HSP70 with viral proteins[J].Virol,1992,66:53-57
[1]李达君,袁君等.NMP238,HSP70在宫颈鳞癌中的表达及意义[J].中国医学工程.2007,15(4):320-322
[2]PARK IN DM,FERLAY F,FERLAY J et al Estinatingthe world cancer burden G lobocan 2000[J].Cancer 2001,94:153-156
[3]廖彩森.宫颈癌流行病学及病因学研究进展[J].实用妇产科杂志.1994,10(5):229-231
[4]李隆玉,李诚信.宫颈癌的预防与普查[J].中国实用妇科杂志.2003,19-151
[5]孙蓉,顾建建,李湘明,等.中国宫颈癌病死率及饮食因素的相关分析[J].中国妇幼保健.2004,19(20):57
[6]Altman JD,Moss PA,Goulde r PJ et al Phenotypic analysis of antigen-specific T lymphocytes[J].Science,1996,274(5284):94-96
[7]Appay V,Row land-Jones SL.The assessment of antigen-specific CD8+T cells through the combination of MHC class Ⅰ tetramer and intracellularstaining[J].J Immunol Methods,2002;268:9-19
[8]Hugues S Malberbe I,Filippi C,et al Gene ration and use of alter native multimers of peptide/MHC complexes[J].J Immunol Methods 2002,268:83-92
[9]王林.β2-微球蛋白在小儿疾病诊治中的研究进展[J].临床儿科杂志.2005,23(12):897-898
[10]许晓倩,王健民.β2-微球蛋在恶性血液病中的临床意义[J].中华血液学杂志2005,26(7):444-446
[11]Bjorkman PJ,SaperMA,SamraouiB,et al Structure of the human class Ⅰhistocompatibility antigen,HLA-A2[J].Nature,1987;329(6139):506-512
[12]Kozlowsk i S,Takeshita T,Boehncke WH,et al Excess beta 2-microglobulin promoting functional peptide association with purified soluble class Ⅰ MHC molecules [J].Nature,1991;349(6304):74-77
[13]Otten GR,Bikoff E,Ribaudo RK,et al Peptide and beta 2-microglobulin regulation of cell surface MHC class Ⅰ conformation and expression[J].J Immunol,1992;148:3723-3732
[14]Shields MJ,Assefi N,Hodgson W,et al Characterization of the interactions between MHC class Ⅰ subunits a systematic approach for the engineering of higher affinity variants of beta 2-microglobulin[J].J Immunol,1998;160:2297-2307
[15]Shields MJ,Kubota R,Hodgson W,et al The effect of human beta 2- microglobulin on major histocom patibility complex Ⅰ peptide loading and the engineering of a high affinity variant Implications for peptide-based vaccines[J].J Biol Chem,1998;273:28010-28018
[16]邓惟德,张育,顾健等.血与尿B2微球蛋白在白血病及其它血液病中的研究[J].临床血液学杂志.1991,16(3):128
[17]郭少磊,王爱英等.血清B2-微球蛋白检测对肾脏疾病及恶性肿瘤的诊断价值[J].齐鲁医学杂志.2006,21(4):355
[18]王林.β2-微球蛋白在小儿疾病诊治中的研究进展[J].临床儿科杂志.2005,23(12):897-898
[19]黄淑华,郭永炼,战熔等.146例次性血液病患者血清B2微球蛋白测定的临床意义[J].中华内科杂志.1993,32(8):558
[20]Burkes RL,Sherrod A,Gill PS et al.Serum Beta-2 Microglubulin Levela in Homosexual Men with AIDS and with Presistend,Generalized Lymphoademyathy[J].Cancer 1986,57(7):2190
[21]托马斯,主编.临床实验诊断学[M].第一版.上海科学技术出版社.2004,657-668
[22]王征.肝硬化患者血、尿B2-微球蛋白检测意义[J].张家口医学院学报.2002,19(5):34
[23]王景萍,邵国庆.肝癌患者B2-微球蛋白检测意义探讨[J].中原医刊.2007,34(10):92
[24]苏丽芳.肿瘤病人血清B2-微球蛋白的测定及其临床意义[J].广州医药.1997,2(2):51
[25]王林.β2-微球蛋白在小儿疾病诊治中的研究进展[J].临床儿科杂志.2005,23(12):897-898
[26]张民军,叶伟民,陆慧琦,等.血、尿B2-微球蛋白在恶性实体瘤诊断中的价值[J].上海医学检验杂志.2001,16(3):169
[27]郑有文,姚立新,吕文臣,等.CA50、CEA、AFP、B2-M联合检测对提高消化道恶性肿瘤诊断率的价值探讨[J].河北医学.1999,5(10):7-9
[28]Hewitt EW,Lehner PJ.The ABC-transporter signature motif Is required for peptide translocation but not peptide binding by TAP[J].Eur Immunol,2003,33(2):422-427.
[29]Ehses S,Leonhardt RM,Hansen G,et al.Functional role of C-terminal sequence elements in the transporter associated With antigen processing[J].J Immunol,2005,174(1):328-339.
[30]Koch J,Guntrum R,Tampe R.Exploring the minimal func Tiona lunit of the transporter associated with antigen proces Sing[J].FEBS Lett,2005,579(20):4413-4416.
[31]Koch J,Guntrum R,Heintke R,et al.Functional dissection Of the taansmembrane domains of the transporter associated With antigen processing(TAP)[J].J Biol Chem,2004,279(11):10142-10147.
[32]Procko E,Raghuraman G,Wiley DC,et al.Identification of Domain boundaries within the N-termini of TAP1 and TAP2 And their importance in tapasin binding and tapasin mediated Increase in peptide loading of MHC class Ⅰ[J].Immunol Cell Biol,2005,83(5):475-482.
[33]Nerrnann L,Tampe R.Kinetic analysis of peptide binding to The TAP transport,complex:evidence for structural rearrange Ments induced by substrate binding[J].J Mol Biol,1999,294(5):1203-1213.
[34]Bouabe H,Knittle rMR.The distinct nucleotide binding States of the transporter asrociated with antigen processing(TAP)are regulated by the nonhomologous C-terminal tails of TAP1 and TAP2[J].Eur J Biochem,2003,270(22):4531-4546.
[35]Karttunen JT,Lehner PJ,Gupta SS,et al.Distinct funct ions And cooperative interaction of the subunits of the transporter Associated with antigen processing(TAP)[J].Proc Natl Acad Sci USA,2001,98(13):7431-7436.
[36]Garbi N,Tiwari N,Momburg F,et al.A major role for Tapasin as a stabilizer of the TAP peptide transporter and conSequences for MHC class Ⅰ expression[J].Eur J Immunol,2003,33(1):264-273.
[37]Whang DH,Park H,Roh EY,et al TAP1 and TAP2 gene Polymorphisms and HLA-TAP haplotypes in Koreans based on 90 families[J].Hum Immunol,2005,66(9):998-1007.
[38]Guerri RA,Cabrera CM,Garrido F,et al.TAP1 and TAP2 Polymorphisms and their linkage disequilibrium with HLA-DR,-DP,and-DQ in anEastem Andalusianpo pulation[J].Human Immunol,2005,66(8):921-930.
[39]Penfornis A,Tuomilehto-Wolf E,Faustman DL,et al.Anal Ysis of TAP2polymorphisms in Finnish individuals with type 1 Diabetes[J].Hum Immunol,2002,63(1):61-70.
[40]Kumagai S,Kanagawa S,Morinobu A,et al.Association of A new allele of the TAP2gene,TAp2*Bky2(Val577)with Susceptibility to Sjogren'.s syndrome[J].Arthritis Rheum,1997,40(9):1685-1692.
[41]Yu MC,Huang CM,Wu MC,et al.Association of TAP2 Gene polymorphisms in Chinese patients with rheumatoid ar-Thritis[J].Clin Rheumatol,2004,23(1):35-39.
[42]Seliger B,Atkins D,Bock M,et al.Characterization of hu Man lymphocyte antigen class Ⅰ antigen pmcessingmachinery Defects in renal cell carcinoma lesions with special emphasis On transporter-associated with antigen-processing down regulation[J].Clin Cancer Res,2003,9(5):1721-1727.
[43]Zhu K,Wang J,Zhu J,et al.p53 induces TAP1 and enHances the transport of MHC class Ipeptides[J].Oncogene.1999,18(54):7740-7747.
[44]Yang T,McNally BA,Ferrone S,et al.Asingle nucleotide Deletion leads to rapid degradation of TAP1 mRNA in amela2 Noma cell line[J].J Biol Chem,2003,278(17):15291-15296.
[45]Vambutas A,Bonagura VR,Steihberg BM.Altered expres-Sion of TAP1 and major histocompatibility complex class Ⅰ in Laryngeal papillomatosis:correlation of TAP1 with disease[J].Clin Diagn Lab Immunol,2000,7(1):79-85.
[46]Koppers Lalic D,Reits EA,Ressing ME,et al.Varicellovir-Uses avoid T cell recognition by UL49.5mediated inactivation Of the transporter associated with antigen processing[J].Proc NatlAcadSciUSA,2005,102(14):5144-5149.
[47]nanbu k,konishi i,komatsut,et al.expression of heat shock proteins hsp70 and hsp70 in endometrial carcinomas,correlation with clinicopathology,sex steroid receptor status,and p53 protein expression.cancer,1996,77:330-338
[48]K M KK,JANE TJ,KM JR Hsp70 and ER expression in cervical intraepithelial neoplasia and cervical cancer[J].J korean Sci 1998,13(4):383
[49]HELLMAN K,ALAIYA AA,SCHEDVNS K,et al Protein expression pattems in primary carcinoma of the vagina J Br J Cancer 2004,91(2):319-326
[50]Wang XP,Qiu FR,Liu GZ,et al Correlation between clinicopathology and expression of heat shock protein 70 and glucose-regulated protein 94 in human colonic adenocarcinoma[J].World J Gastroenterol,2005,11(70:1056-1059
[51]Lebret T,W atson RW,Molinie V.Heat shock proteins HSP27,HSP60,HSP70 and hsp90:expression in lbadder carcinomal[J].Cancer,2003,98(5):970-977
[52]VanmuylderN,Evrard L,Daelemans P.Expression of heat shock proteins in salivary gland tumors Immunohistochemical studay of HSP27,HSP70,HSP90,HSP110:apropos of 50 cases[J].Ann Pathal,2000,20(3):190-195
[53]Kim KK,Jang TJ,Kim JT.HSP70 and ER expression in cervical intraepithelial neoplasia and cervical cancer[J].J Korean Med Sci,1998,13(4):383-388
[54]wei yq,zhao x,kariya y,et al.inhibition of proliferation and induction of apoptosis by abrogation of heat-shock protein(hsp70)expression in tumor cell[J],cancer immunol immunother,1995,40:73-78
[55]Tjalma WA,Weyler JJ,Bogers JJ,et al.The importance of biological factors(bcl-2,bax,p53,PCNA,MI,HPV and angiogenesis)in invasive cervical cancer[J].Eur J Obstet Gynecol Reprod Biod,2001,97(2):223-230
[56]李达君,袁君,等.NMP238,HSP70在宫颈鳞癌中的表达及意义[J].中国医学工程.2007,15(4):320-326
[57]Yang Q,Sakurai T,Yoshimura G,et al Prognostic value of Bcl-2 in invasive breast cancer receiving chemotherapy and endocring therapy[J].Oncol Rep,2003,10(1):121-125
[58]Eur J.Long-term prognostic significance of HSP70 C-myc and HLA DR expression in patients with malignant melanoma[J]Eur J Surg Oncol,2001,27(1):88-93
[59]GUO YH,TIAN XY,MI JQ,et al Expression and significance of HSP70 and Bcl-2 in cervical squanous cell cancer[J].Shandong Medical Joumal.2006,46(24):11-12.Chinese
[60]郭云鸿,田晓予,等.热休克蛋白70和热休克蛋白27在宫颈鳞癌中的表达及其意义[J].中原医刊.2006,33(24):4-6
[61]陈向敏,夏克栋,等.HSP70、P53、Bcl-2在宫颈癌组织中的表达及其与人乳头瘤病毒感染的关系[J].温州医学院学报.2004,34(4):288-289
[62]Carvalho MG,Fournier MV.Effect of heat shocd on gene expression of aedes albopictus cell infected with mayaro virus[J].Res Virol,1991,142:25
[63]Jindal S,Young PA,Vaceinia virus infetion induces a stress response that leads to association of HSP70 with viral proteins[J].Virol,1992,66:53-57
[64]傅国庆,郭仁宣,姚振宇,等.月中瘤热休克蛋白70多肤复合物诱导特异性细胞毒T淋巴细胞产生的实验研究[J].中华医学杂志.2000,80(4):301-303
[65]Casey DG,Lysaght J,James T,et al Heat shock protein derived from a non-autologous tumour can be used as an anti-tumour vaccine[J].Immunology,2003,,110:105-111