“****”研究员确定食道癌发病新机制

　　

生物通报道：癌症的发病机制一向为人关注。最近，中科院上海生命科学研究院营养科学研究所的一项最新研究发现，一对爱玩“推手游戏”的“兄弟”分子可能参与了食管癌发生发展的全过程，一旦正方“失手”，就可能造成细胞癌变。

 

据该课题负责人谢东介绍，人体正常情况下，“正方”与免疫相关的分子IRF-1含量较高，它能“扶持”干扰素在细胞中起作用，抵抗病毒感染以及具有癌变倾向细胞的生长。而“反方”IRF-2则抑制干扰素，间接“助纣为虐”。正是这对“兄弟”“你推我挡”的“游戏”，使人体维持微妙的平衡。一旦“正方”长期处于弱势，邪恶的IRF-2就会帮助病毒得寸进尺地“侵蚀”健康细胞，使肌体炎症长期难以恢复，最终导致细胞生长失控，发生癌变。

 

研究人员通过对临床标本的分析发现，食管癌组织中，这一正一邪两“兄弟”明显“势力”不均：IRF-2占据强势，表达量明显增多，而IRF-1则远远败落下风。因此，研究组成员推测，有可能是食管慢性炎症导致IRF-2积累，逐渐使得细胞调控失常，最终发生癌变。

 

此外，通过对不同级别食管癌的蛋白表达的分析，一些与发病相关的特异分子首次“浮出水面”。谢东表示，如果应用到临床实践，这项技术可从分子层面进行辅助诊断。到那时，食管癌早期检出率将大大提高。而且，发现后还可帮助准确分级，根据病程不同，采用不同治疗方法。据悉，相关论文已被国际权威刊物《癌症研究》和《蛋白质组学》接受。

 

谢东

 

2003年 8月 入选中国科学院 “****”

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2001年 5月 获美国淋巴瘤基金会人才基金
1997年 5月 获美国南卡罗来纳州州立大学凯瑟琳遗传学奖

 

1.      受教育简况：
1992. 8-1997. 5 美国南卡罗来纳州州立大学生物系攻读分子生物学博 士学位。
1986. 9-1989. 7 中国科学院遗传所攻读分子遗传学硕士学位。
1979. 9-1983. 7 江西大学生物系读本科，获学士学位。

2. 科研工作经历：
2003. 1-至今 中国科学院上海生命科学研究院营养所研究员、 研究组长。
2002. 4-2004. 2 美国加州大学洛杉矶分校(UCLA)医学院助理教授。
2000. 4-2002. 4 美国加州大学洛杉矶分校西赛医学中心研究员。
1997. 5-2000. 4 美国加州大学洛杉矶分校西赛医学中心做博士后研究。

 发表论文情况：

1. Dong Xie, Dong Yin, Xiangjun Tong, James O’Kelly, Carl Miller, Johathan W. Said, Keith Black and H. Phillip Koeffler. Cyr61 is Overexpressed in Gliomas and Involved in Integrin Linked Kinase Mediated Akt and β-Catenin-TCF/Lef Signaling Pathways. Cancer Research, 64: 1987-1996, 2004

2. Dong Xie, Dong Yin, Heming Wang, Gentao Liu, Robert Elashoff, Keith Black and H. Phillip Koeffler. Levels of expression of Cyr61 and CTGF are prognostic for tumor progression and survival of individuals with Gliomas. Clinical Cancer Research, 10(6), 2072-2081, 2004

3. Tong Xiangjun, James O’Kelly, Dong Xie, Carston Miller, Carl Miller, H. Phillip Koeffler and. Cyr61 suppresses the growth of non-small cell lung cancer cells via the -catenin-c-myc-p53 pathway. Oncogene, 1-9, 2004.

4. Dong Yin, Dong Xie, Seven DeVos, Gentao Liu, Carl Miller, Keith Black and Phillip Koeffler. Imprinting status of DLK1 gene in brain tumors and lymphomas. International Journal of Oncology, 24 (4), 1011-1016, 2004.

5. Gentao Liu, John S. Yu, Gang Zeng , Dong Yin , Dong Xie, Paul F. Robbin, Keith L. Black , and Han Ying. Expression and functional analysis of a novel melanoma –associated antigen: AIM-2 as immunotherapeutic target in malignant glioma, Journal of Immunotherapy, 27(3):220-226, 2004

6. Tong Xiangjun, Dong Xie, Wilfried Roth, John Reed, and H. Phillip Koeffler. NADE (p75NTR-associated cell death executor) Suppresses Cellular Growth in vivo. International Journal of Oncology. 22: 1357-1362, 2003

7. Sigal Gery, Dong Yin, Dong Xie, Keith Black and Phillip Koeffler. TMEFF1 and brain tumors. Oncogene. 22(18):2723-7, 2003

8. Dong Yin, Dong Xie, Wolf-karsten Hofmann, Kamlesh Asotra, Rex Wong, Keith L. Black and H. Phillip Koeffler. Promoter Hypermethylation of DNA repair gene O6-methylguanine-DNA methyltransferase is associated with its Downregulation and GC to A:T mutation of p53 in brain tumors. Molecular Carcinogenesis. 36:23-31, 2003.

9. Dong Xie, Anna Jauch, Carl W. Miller, Claus R. Bartram and H. Phillip Koeffler. Discovery of over-expressed genes and genetic alterations in breast cancer cells using a combination of suppression subtractive hybridization, M-FISH and comparative genomic hybridization. International Journal of Oncology. 21(3) 499-507, 2002

10. Dong Yin, Dong Xie, Wolf-Karsten Hofmann, Carl W. Miller, Keith L Black and H. Phillip Koeffler. Methylation, expression, mutation of the cell cycle control genes in human brain tumors. Oncogene 21(54):8372-8, 2002.

11. Gabor Szalai, Dong Xie, Michele Wassenich, Monika Veres, Jeffrey D. Ceci, Michael J. Dewey, Andrei Molotkoy, Gregg Duester and Michael R. Felder. Distal and proximal cis-linked sequences are needed for the total expression phenotype of the mouse alcohol dehydrogenase 1 (Adh1) gene. Gene. 29;291(1-2):259-70, 2002.

12. Dong Xie , Kei Nakachi, Heming Wang, Robert Elashoff and H. Phillip Koeffler. Elevated levels of CTGF, WISP-1 and Cyr61 in primary breast cancers associated with more advanced features. Cancer Research. 61(24), 8868-8876, 2001.

13. Dong Xie, Carl W. Miller, James O'Kelly, Kei Nakachi, Akiko Sakashita, Johathan W. Said, Jeffrey Gornbein and Phillp Koeffler. Breast Cancer: Cyr61 is over-expressed, estrogen inducible and associated with more advanced disease. J. Biol. Chem. 276 (17), 14187–14194, 2001.

14. Xiangjun Tong, Dong Xie, James O'Kelly, Carsten Muller, Carl Miller and H. Phillip Koeffler. Cyr61, a member of CCN family, is a tumor suppressor in non-small cell lung cancer. J. Biol. Chem. 276 (50), 47709-47714, 2001.

15. Wolf-K. Hofmann, Seisho Takeuchi, Dong Xie, Carl W. Miller, Dieter Hoelzer and H. Phillip Koeffer. Frequent loss of heterozygosity in the region of D1S450 at 1p36.2 in myelodysplastic syndromes. Leukemia Research 10:855-8, 2001.

16. Dong Xie, Wilhelem K. Hofmann, Naoki Mori, Carl Miller, Dieter Hoelzer and H. Phillip Koeffler. Allelotype Analysis of the Myelody splastic Syndrome. Leukemia 14(5), 805-10, 2000.

17. Dong Xie, Purnima Narasimhan, Yao-Wu Zheng, Michael Dewey and Michael R. Felder. Ten Kilobases of 5’-flanking region confers proper regulation of the mouse alcohol dehydrogenase (Adh-1) gene in kidney and adrenal of transgenic mice. Gene 181, 173-178, 1996.

18. Dong Yin, Dong Xie, Sven de Vos, Carl W. Miller, Keith L Black and H. Phillip Koeffler. Maintenance of Normal Imprinting of DLK1 Gene in Brain Tumors and Lymphomas (submitted).