卵巢癌组织及细胞株中肿瘤特异性抗原MAGE、GAGE、BAGE基因表达的研究
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摘要
目的 观察卵巢上皮性癌组织及肿瘤细胞株中肿瘤特异性抗原MAGE、BAGE、GAGE基因的表达，以探讨基因表达与诊疗、预后的关系，评价基因产物作为卵巢癌标志物以及卵巢癌免疫治疗靶位的可行性。同时研究5—杂氮脱氧胞嘧啶(DAC)对卵巢癌细胞株SKOV3、A2780、COC1增殖和肿瘤特异性抗原MAGE、BAGE、GAGE表达的影响。
方法 采用RT—PCR分析10例正常卵巢、20例卵巢良性肿瘤、47例卵巢上皮性癌组织及三种卵巢癌细胞株SKOV3、A2780、COC1中MAGE-1、MAGE-3、GAGE-1／2及BAGE基因mRNA水平的表达。同时将处于对数生长期的卵巢癌细胞系与5-杂氮脱氧胞嘧啶(DAC)共同培养，观察细胞生长指数并利用流式细胞术检测细胞周期变化及凋亡情况；应用RT-PCR法检测卵巢癌细胞株SKOV3、A2780、COC1在DAC作用前后肿瘤特异性抗原MAGE、BAGE、GAGE表达的变化。
结果 正常卵巢组织中MAGE、GAGE、BAGE基因无表达，良性肿瘤中仅有基因MAGE-1表达，阳性率为15％(3／20)。卵巢癌组织MAGE-1、MAGE-3的表达率较高，分别为51.1％(25／47)、34％(16／47)，GAGE-1／2及BAGE基因在卵巢癌组织中的表达率分别为25.5％(12／47)和14.9％(7／47)。卵巢癌转移灶仅有MAGE-1、BAGE基因表达，阳性表达率分别为28.6％(2／7)、14.3％(1／7)。浆液性囊腺癌标本中MAGE-1、MAGE-3的阳性表达率分别为77.8％、66.7％，明显高于其它类型卵巢恶性肿瘤中的表达率，差异有显著性(P＜0.05)。尽管GAGE-1／2及BAGE基因在卵巢癌组织中的表达率相对较低，但在浆液性囊腺癌中仍有相对较高的阳性表达率。
基因的表达与绝经及有无淋巴结转移无关，MAGE-1、MAGE-3的阳性表达与卵巢癌患者的病理分级及临床分期呈正相关，差异有显著性(P＜0.05)，而BAGE、GAGE-1／2
Objective To observe the expression of MAGE, BAGE and GAGE gene in ovarian cancer tissue and cell line ; To investigate the effect of 5-aza-2 ' -deoxycytidine in proliferation of ovarian cancer cell line and expression of tumor specific antigen MAGE BAGE GAGE.
Methods The expression levels of MAGE-1、 MAGE-3、 GAGE-1/2 and BAGE was detected by reverse transcription polymerase chain reaction(PT-PCR) in ovarian cancer cell line SKOV3、 A2780、COC1 ,and 10 cases of normal ovarian tissues, 20 cases of benign epithelial tumor, 47 cases of malignant epithelial tumor ; Ovarian cancer cell were treated with 5-aza-2' -deoxycytidine(DAC) in co-culture, the growth curves were observed; the cell cycle was detected by flow cytometry(FCM);the gene expression pattern before and after drug treatment was measured by RT-PCR.
Results Normal ovarian tissue does not express members of the gene families studied. In 3/20 benign tumor tissue specimens expressed MAGE-1.The ovarian cancer tissue samples expressed MAGE-1、MAGE-3、GAGE-1/2 and BAGE in 51.1% (25/47)、 34% (16/47) , 25.5% (12/47) and 14.9% (7/47) .A total of 2/7 metastatic lesions from ovarian carcinoma expressed MAGE-1 and one expressed BAGE. There is preferential expression of the
方法 采用RT—PCR分析10例正常卵巢、20例卵巢良性肿瘤、47例卵巢上皮性癌组织及三种卵巢癌细胞株SKOV3、A2780、COC1中MAGE-1、MAGE-3、GAGE-1／2及BAGE基因mRNA水平的表达。同时将处于对数生长期的卵巢癌细胞系与5-杂氮脱氧胞嘧啶(DAC)共同培养，观察细胞生长指数并利用流式细胞术检测细胞周期变化及凋亡情况；应用RT-PCR法检测卵巢癌细胞株SKOV3、A2780、COC1在DAC作用前后肿瘤特异性抗原MAGE、BAGE、GAGE表达的变化。
结果 正常卵巢组织中MAGE、GAGE、BAGE基因无表达，良性肿瘤中仅有基因MAGE-1表达，阳性率为15％(3／20)。卵巢癌组织MAGE-1、MAGE-3的表达率较高，分别为51.1％(25／47)、34％(16／47)，GAGE-1／2及BAGE基因在卵巢癌组织中的表达率分别为25.5％(12／47)和14.9％(7／47)。卵巢癌转移灶仅有MAGE-1、BAGE基因表达，阳性表达率分别为28.6％(2／7)、14.3％(1／7)。浆液性囊腺癌标本中MAGE-1、MAGE-3的阳性表达率分别为77.8％、66.7％，明显高于其它类型卵巢恶性肿瘤中的表达率，差异有显著性(P＜0.05)。尽管GAGE-1／2及BAGE基因在卵巢癌组织中的表达率相对较低，但在浆液性囊腺癌中仍有相对较高的阳性表达率。
基因的表达与绝经及有无淋巴结转移无关，MAGE-1、MAGE-3的阳性表达与卵巢癌患者的病理分级及临床分期呈正相关，差异有显著性(P＜0.05)，而BAGE、GAGE-1／2
Objective To observe the expression of MAGE, BAGE and GAGE gene in ovarian cancer tissue and cell line ; To investigate the effect of 5-aza-2 ' -deoxycytidine in proliferation of ovarian cancer cell line and expression of tumor specific antigen MAGE BAGE GAGE.
Methods The expression levels of MAGE-1、 MAGE-3、 GAGE-1/2 and BAGE was detected by reverse transcription polymerase chain reaction(PT-PCR) in ovarian cancer cell line SKOV3、 A2780、COC1 ,and 10 cases of normal ovarian tissues, 20 cases of benign epithelial tumor, 47 cases of malignant epithelial tumor ; Ovarian cancer cell were treated with 5-aza-2' -deoxycytidine(DAC) in co-culture, the growth curves were observed; the cell cycle was detected by flow cytometry(FCM);the gene expression pattern before and after drug treatment was measured by RT-PCR.
Results Normal ovarian tissue does not express members of the gene families studied. In 3/20 benign tumor tissue specimens expressed MAGE-1.The ovarian cancer tissue samples expressed MAGE-1、MAGE-3、GAGE-1/2 and BAGE in 51.1% (25/47)、 34% (16/47) , 25.5% (12/47) and 14.9% (7/47) .A total of 2/7 metastatic lesions from ovarian carcinoma expressed MAGE-1 and one expressed BAGE. There is preferential expression of the
引文
1. Van den Eynde B, Peeters O, De Backer O, et al. A new family of genes coding for an antigen recognized by autologous cytolytic T lymphocytes on a human melanoma. J Exp Med. 1995, 182(3): 689-698.
2. Weber J, Salgaller M, Samid D, et al. Expression of the MAGE-1 tumor antigen is upregulated by the demethylating agent 5-aza-2'-deoxytidine. Cancer Res, 1994, 54(7): 1766-1771.
3．卢学春，楼方定，许周敏等。去甲基化和组蛋白去乙酰化转移酶抑制剂对K562细胞增殖和肿瘤相关基因表达的影响。中国实验血液学杂志，2004，12(1)：44—47．
4．马鸣，俞莉章，那彦群。肿瘤特异性抗原MAGE基因的表达及意义。国外医学泌尿系统分册，2003，23(5)：526—529．
5. Van der Bruggen P, Traversari C, Chomze P, et al. A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. Science, 1991, 25: 1643-1647.
6. Boel P, Wildmann C, et al. BAGE: A new gene encoding an antigen recognized on a human melanoma by cytolytic T lymphocytes. Immunity, 1995, 2: 167-165.
7. Li M, Yuan YH, Han Y, Liu YX, et al. Expression profile of cancer-testis genes in 121 human colorectal cancer tissue and adjacent normal tissue. Clin Cancer Res, 2005 Mar 1, 11(5): 1809-1814.
8. Kayashi Y, Nouso K, et al. Expression of MAGE, GAGE and BAGE genes in human liver disease: utility as molecular markers for hepatocellular carcdnoma. J Hepatol, 2000, 32.. 612-617.
9. Mori M, Inoue H, Mimori K, et al. Expression of MAGE genes in human eolorectal carcinoma. Ann Surg, 1996, 224: 183-188.
10. Fujie T, Mori M, Ceo H, et al. Expression of MAGE and BAGE genes in Janpanese breast cancers. Ann Oncol, 1997, 17: 3559-3563.
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27. Schlott T, Ahrens K, Ruschenburg I, et al. Different gene expression of MDM2, GAGE-1, -2 and FHIT in hepatocellular carcinoma and focal nodular hyperplasia. Br J Cancer, 1999, 80(1-2): 73-78.
28. Yamashita N, Ishibashi H, Hayashida K, et al. High frequency of the MAGE-1 gene expression in hepatocellular carcinoma. Hepatology, 1996, 24: 1437-1440.
29. Chitale DA, Jungbluth AA, Marshall DS, Leitao MM et al. Expression of cancer-testis antigens in endometrial carcinomas using a tissue microarray [J]. Mod Pathol, 2005 Jan, 18: 119-126.
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31. Hee-Kyung Chang, JongWook Park, WooGyeong Kim, et al. The expression of MAGE and GAGE genes in uterine cervical carcinoma of Korea by RT-PCR with common primers. Gynecol Oncol, 2005, 97: 342—347.
32. Russo V, Dalerba P, Ricci A, Bonazzi C, et al. MAGE, BAGE and GAGE genes experiences in fresh epithelial ovarian carcinomas. Int J Cancer, 1996, 67(3): 457-460.
33. Gillespie AM, Rodgers S, Wilson AP, et al. MAGE, BAGE and GAGE: tumor antigen expression in begin and malignant ovarian tissue. Br J Cancer, 1998, 78(6): 816-821.
34. Hofmann M, Ruschenburg I mRNA detection of tumor-rejection genes BAGE, GAGE, and MAGE in peritoneal fluid from patients with ovarian carcinoma as a potential diagnostic tool. Cancer Cytopathology, 2002, 96(3): 187-193.
35．葛海良，王颖，刘文文，等．人卵巢癌中三种MAGE家族基因表达和患者HLA 表型的初步分析．上海免疫学杂志，2001，21(4)：234-236．
36．张颖，王吉耀，刘天舒．MAGE基因在消化道肿瘤的表达[J]．国外医学消化系疾病分册，2003，23(4)：248-250．
37.. Kufer P, Zippelius A, Lutterbuse R, et al. Heterogeneous expression of M AGE-A genes in occult dissemimated tun'lor cells: anovel mulimarker reverse transcription-polymerase chain reactionfor diagnosis of micrometastatic disease[J]. Cancer Res, 2002, 62(11): 251～261.
38. Miyamoto A, Fujiwara Y, Sakon M, et al. Development of a multiple-marker RT-PCR assay for detection of micrometastases of hepatocellular carcinoma. Dig Dis Sci, 2000, 45 (7): 1376—1382.
39. Mou DC, Cai SL, Peng JR, et al. Evaluation of MAGE-1 and MAGE-3 as tumour-specific markers to detect blood dissemination of hepatocellular carcinoma cells. Br J Cancer, 2002, 86(1): 110—116.
40．李芳 朱怀仕 贾平，等．卵巢癌患者自体肿瘤细胞疫苗的临床应用．中华妇产科杂志，2004，39(1)：51—52．．
41. Dalerba P, Ricci A, Russo V, et al. High homogeneity of MAGE, BAGE, GAGE, Tyrosinase and Melan-A/MART-1 gene expression in clusters of multiple simul-taneous metastases of human melanoma: Implications for protocol design of therapeutic antigen-specific vaccination strategies. Int J Cancer, 1998, 77(2): 200-204.
42. Dalerba P, Frascella E, Macino B, et al. MAGE, BAGE and GAGE gene expression in human rhabdomyosarcomas. Int J Cancer, 2001, 93: 85-90.
43. Miyashiro I, Kuo C, nuynh K, et al. Molectflar strategy for de-tecting metastatic cancer with use of multiple tumor-specificMAGE-A genes[J]. Clin Chem, 2001, 47(3): 505～512.
44. Thumer B, Haendle I, Roder C, et al. Vaccination with MAGE-3Alpep-tidepulsed mature, monocyte2derived dendritic cells expands specific cytotoxic T cells and induces regression of some metastases in advanced stage IV melanoma. J Exp Med, 1999, 190(11): 1669-1678.
45. Marchand M, VanBaran N, Weynants P, et al. Tumor regressions observed in patients with metastatic melanomna treated with an antigenic peptide encoded by gene MAGE-3 and presented by HLA-Al. Int J Cancer, 1999, 80: 219～230.
46. Chaux P, Vantomme V, Boon T, et al. Identification of MAGE-3 Epitopes Presented by HLA-DR Molecules to CD4(?)+ T Lymphocytes. J Exp Med, 1999, 189(5). 767-778.
47. Mortarini R, Anichini A, Di Nicola M, et al. Cytotoxic T cells directed to tumor antigens not expressed on normal melanocytes dominate HLA-A2.1-restricted immune repertoire to melanoma. J Immunol, 1996, 156(1): 208-217.
48．刘庆伦，张昌卿，冯凯涛．非小细胞肺癌MAGE-3基因产物的表达[J]．中华肿瘤杂志，2002，22(2)：138～140．
49. Traversari C, Meazza R, Copplecchia M, et al. IFN-7 gene transfer restores HLA-class I expression and MAGE-3 antigen presentation to CTL in HLA-deficient small cell lung cancer. Gene Ther, 1997, 4: 1029～1035.
50．耿淼，吴玉章，万瑛．肿瘤抗原MAGE—A家族成员进化关系的初步研究[J]．中国免疫学杂志，2002，18(5)：341～344．
51. Olivier De Backer, Karen C, et al. Characterization of the GAGE Genes That Are Expressed in Various Human Cancers and in Normal Testis. Cancer Res, 1999, 59(13): 3157-3165.
1. Van den Eynde B, Peeters O, De Backer O, et al. A new family of genes coding for an antigen recognized by autologous cytolytic T lymphocytes on a human melanoma. J Exp Med, 1995, 182(3): 689-698.
2．马鸣，俞莉章，那彦群．肿瘤特异性抗原MAGE基因的表达及意义．国外医学泌尿系统分册，2003，23(5)：526—529．
3. Van der Bruggen P, Traversari C, Chomze P, et al. A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. Science, 1991, 25: 1643-1647.
4. Boel P, Wildmann C, et al. BAGE: A new gene encoding an antigen recognized on a human melanoma by cytolytic T lymphocytes. Immunity, 1995, 2: 167-165.
5. Li J, Yang Y, Fujie T, et al. Expression of MAGE, GAGE and BAGE genes in human gastric carcinoma. Clin Cancer Res, 1996, 2: 1619-1625.
6. Russo V, Dalerba P, Ricci A, Bonazzi C, et al. MAGE, BAGE and GAGE genes experiences in fresh epithelial ovarian carcinomas. Int J of Cancer, 1996, 67(3): 457-460.
7. Gillespie AM, Rodgers S, Wilson AP, et al. MAGE, BAGE and GAGE: tumor antigen expression in begin and malignant ovarian tissue. Br J of Cancer, 1998, 78(6): 816-821.
8. Hofmann M, Ruschenburg I. mRNA detection of tumor-rejection genes BAGE, GAGE, and MAGE in peritoneal fluid from patients with ovarian carcinoma as a potential diagnostic tool. Cancer Cytopathology, 2002, 96(3): 187-193.
9．葛海良，王颖，刘文文，等．人卵巢癌中三种MAGE家族基因表达和患者HLA表型的初步分析．上海免疫学杂志，2001，21(4)：234-236．
10．张颖，王吉耀，刘天舒．MAGE基因在消化道肿瘤的表达[J]．国外医学消化系疾病分册，2003，23(4)：248-250．
11. Kufer P, Zippelius A, Lutterbuse R, et al. Heterogeneous expression ofM AGE-A genes in occult dissemimated tun'lor cells: anovel mulimarker reverse transcription-polymerase chain reactionfor diagnosis of micrometastatic disease[J]. Cancer Res, 2002, 62(11): 251～261.
12. Miyamoto A, Fujiwara Y, Sakon M, et al. Development of a multiple-marker RT2PCR assay for detection of micrometastases of hepatocellular carcinoma. Dig Dis Sci, 2000, 45 (7): 1376-1382.
13. Mou DC, Cai SL, Peng JR, et al Evaluation of MAGE-1 and MAGE-3 as tumour-specific markers to detect blood dissemination of hepatocellular carcinoma cells. Br J Cancer, 2002, 86(1): 110-116.
14．李芳，朱怀仕，贾平，等．卵巢癌患者自体肿瘤细胞疫苗的临床应用．中华妇产科杂志，2004，39(1)：51—52．
15. Dalerba P, Ricci A, Russo V, et al. High homogeneity of MAGE, BAGE, GAGE, Tyrosinase and Melan-A/MART-1 gene expression in clusters of multiple simultaneous metastases of human melanoma: Implications for protocol design of therapeutic antigen-specific vaccination strategies. Int J of Cancer, 1998, 77(2): 200-204.
16. Dalerba P, Frascella E, Macino B, et al. MAGE, BAGE and GAGE gene expression in human rhabdomyosarcomas. Int J Cancer, 2001, 93: 85-90.
17. Miyashiro I, Kuo C, nuynh K, et al. Molectflar strategy for de-tecting metastatic cancer with useofmultiple tumor-specifieMAGE-A genes[J]. ClinChem, 2001, 47(3): 505～512.
18. Thurner B, Haendle I, Roder C, et al. Vaccination with MAGE-3Al peptidepulsed mature, monocyte2derived dendritic cells expands specific cytotoxic T cells and induces regression of some metastases in advanced stage Ⅳ melanoma. J Exp Med, 1999, 190(11): 1669-1678.
19. Marchand M, vanBaran N, Weynants P, et al. Tumor regressions observed in patients with metastatic melanomna treated with an antigenic peptide encoded by gene MAGE-3 and presented by HLA-Al. Int J Cancer, 1999, 80: 219～230.
20. Chaux P, Vantomme V, Boon T, et al. Identification of MAGE-3 Epitopes Presented by HLA-DR Molecules to CD4(?)+ T Lymphocyte. J of Exp Med. 1999, 189(5): 767-778.
21. Mortarini R, Anichini'A, Di Nicola M, et al. Cytotoxie T cells directed to tumor antigens not expressed on normal melanoeytes dominate HLA-A2.1-restricted immune repertoire to melanoma. J of Immunol, 1996, 156(1): 208-217.
22．刘庆伦，张昌卿，冯凯涛．非小细胞肺癌mGE-3基因产物的表达[J]．中华肿瘤杂 志，2002，22(2)：138～140．
23. Traversari C, Meazza R, Copplecchia M, et al. IFN-γ gene transfer restores HLA-class Ⅰ expression and MAGE-3 antigen presentation to CTL in HLA-defieient small cell lung cancer. Gene Ther, 1997, 4: 1029～1035.
24．耿淼，吴玉章，万瑛．肿瘤抗原MAGE—A家族成员进化关系的初步研究[J]．中国免疫学杂志，2002，18(5)：341～344．
25. Serrano A, Tanzarella S, et al. Rexpression of HLA class Ⅰ antigens and restoration of antigen-specific CTL response in melanoma cells following 5-aza-2-deoxyeytidine treatment[J]. Int J Cancer; 2001, 94(2): 243-251.
26. Russo V, Dalerba P, Ricci A, Bonazzi C, et al. MAGE, BAGE and GAGE genes experiences in fresh epithelial ovarian carcinomas. Int J of Cancer, 1996, 67(3): 457-460.
27. Olivier De Backer, Karen C, et al. Characterization of the GAGE Genes That Are Expressed in Various Human Cancers and in Normal Testis. Cancer Res,1999, 59(13): 3157-3165.
2. Weber J, Salgaller M, Samid D, et al. Expression of the MAGE-1 tumor antigen is upregulated by the demethylating agent 5-aza-2'-deoxytidine. Cancer Res, 1994, 54(7): 1766-1771.
3．卢学春，楼方定，许周敏等。去甲基化和组蛋白去乙酰化转移酶抑制剂对K562细胞增殖和肿瘤相关基因表达的影响。中国实验血液学杂志，2004，12(1)：44—47．
4．马鸣，俞莉章，那彦群。肿瘤特异性抗原MAGE基因的表达及意义。国外医学泌尿系统分册，2003，23(5)：526—529．
5. Van der Bruggen P, Traversari C, Chomze P, et al. A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. Science, 1991, 25: 1643-1647.
6. Boel P, Wildmann C, et al. BAGE: A new gene encoding an antigen recognized on a human melanoma by cytolytic T lymphocytes. Immunity, 1995, 2: 167-165.
7. Li M, Yuan YH, Han Y, Liu YX, et al. Expression profile of cancer-testis genes in 121 human colorectal cancer tissue and adjacent normal tissue. Clin Cancer Res, 2005 Mar 1, 11(5): 1809-1814.
8. Kayashi Y, Nouso K, et al. Expression of MAGE, GAGE and BAGE genes in human liver disease: utility as molecular markers for hepatocellular carcdnoma. J Hepatol, 2000, 32.. 612-617.
9. Mori M, Inoue H, Mimori K, et al. Expression of MAGE genes in human eolorectal carcinoma. Ann Surg, 1996, 224: 183-188.
10. Fujie T, Mori M, Ceo H, et al. Expression of MAGE and BAGE genes in Janpanese breast cancers. Ann Oncol, 1997, 17: 3559-3563.
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7. Gillespie AM, Rodgers S, Wilson AP, et al. MAGE, BAGE and GAGE: tumor antigen expression in begin and malignant ovarian tissue. Br J of Cancer, 1998, 78(6): 816-821.
8. Hofmann M, Ruschenburg I. mRNA detection of tumor-rejection genes BAGE, GAGE, and MAGE in peritoneal fluid from patients with ovarian carcinoma as a potential diagnostic tool. Cancer Cytopathology, 2002, 96(3): 187-193.
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13. Mou DC, Cai SL, Peng JR, et al Evaluation of MAGE-1 and MAGE-3 as tumour-specific markers to detect blood dissemination of hepatocellular carcinoma cells. Br J Cancer, 2002, 86(1): 110-116.
14．李芳，朱怀仕，贾平，等．卵巢癌患者自体肿瘤细胞疫苗的临床应用．中华妇产科杂志，2004，39(1)：51—52．
15. Dalerba P, Ricci A, Russo V, et al. High homogeneity of MAGE, BAGE, GAGE, Tyrosinase and Melan-A/MART-1 gene expression in clusters of multiple simultaneous metastases of human melanoma: Implications for protocol design of therapeutic antigen-specific vaccination strategies. Int J of Cancer, 1998, 77(2): 200-204.
16. Dalerba P, Frascella E, Macino B, et al. MAGE, BAGE and GAGE gene expression in human rhabdomyosarcomas. Int J Cancer, 2001, 93: 85-90.
17. Miyashiro I, Kuo C, nuynh K, et al. Molectflar strategy for de-tecting metastatic cancer with useofmultiple tumor-specifieMAGE-A genes[J]. ClinChem, 2001, 47(3): 505～512.
18. Thurner B, Haendle I, Roder C, et al. Vaccination with MAGE-3Al peptidepulsed mature, monocyte2derived dendritic cells expands specific cytotoxic T cells and induces regression of some metastases in advanced stage Ⅳ melanoma. J Exp Med, 1999, 190(11): 1669-1678.
19. Marchand M, vanBaran N, Weynants P, et al. Tumor regressions observed in patients with metastatic melanomna treated with an antigenic peptide encoded by gene MAGE-3 and presented by HLA-Al. Int J Cancer, 1999, 80: 219～230.
20. Chaux P, Vantomme V, Boon T, et al. Identification of MAGE-3 Epitopes Presented by HLA-DR Molecules to CD4(?)+ T Lymphocyte. J of Exp Med. 1999, 189(5): 767-778.
21. Mortarini R, Anichini'A, Di Nicola M, et al. Cytotoxie T cells directed to tumor antigens not expressed on normal melanoeytes dominate HLA-A2.1-restricted immune repertoire to melanoma. J of Immunol, 1996, 156(1): 208-217.
22．刘庆伦，张昌卿，冯凯涛．非小细胞肺癌mGE-3基因产物的表达[J]．中华肿瘤杂 志，2002，22(2)：138～140．
23. Traversari C, Meazza R, Copplecchia M, et al. IFN-γ gene transfer restores HLA-class Ⅰ expression and MAGE-3 antigen presentation to CTL in HLA-defieient small cell lung cancer. Gene Ther, 1997, 4: 1029～1035.
24．耿淼，吴玉章，万瑛．肿瘤抗原MAGE—A家族成员进化关系的初步研究[J]．中国免疫学杂志，2002，18(5)：341～344．
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26. Russo V, Dalerba P, Ricci A, Bonazzi C, et al. MAGE, BAGE and GAGE genes experiences in fresh epithelial ovarian carcinomas. Int J of Cancer, 1996, 67(3): 457-460.
27. Olivier De Backer, Karen C, et al. Characterization of the GAGE Genes That Are Expressed in Various Human Cancers and in Normal Testis. Cancer Res,1999, 59(13): 3157-3165.