谢东
肿瘤发生和发展的分子机制研究,主要针对在中国具有很高发病率及死亡率的肺癌、食管癌、胃癌、肝癌,还有虽然发病率不高但恶性程度却极高的大脑胶质细胞瘤。目前工作集中于CCN家族和Eph/ephrin家族分子在上述肿瘤中的作用机理和信号通路的研究。
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- 姓名:谢东
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学术头衔:
“973”、“863”首席科学家, 博士生导师, 国家杰出青年科学基金获得者
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光学
- 研究兴趣:肿瘤发生和发展的分子机制研究,主要针对在中国具有很高发病率及死亡率的肺癌、食管癌、胃癌、肝癌,还有虽然发病率不高但恶性程度却极高的大脑胶质细胞瘤。目前工作集中于CCN家族和Eph/ephrin家族分子在上述肿瘤中的作用机理和信号通路的研究。
谢东教授,男,1962年11月生,博士,研究员,博士生导师。1983年7月毕业于江西大学生物系,获学士学位;1989年7月毕业于中国科学院遗传所,获分子遗传学硕士学位;1997年5月毕业于美国南卡罗来纳州州立大学生物系,获博士学位。1997年5月至2001年4月,在美国加州大学洛杉矶分校西赛医学中心做博士后;2001年4月至2003年5月,美国加州大学洛杉矶分校(UCLA)医学院助理教授;2003年5月至今,中科院上海生命科学研究院营养所研究员、研究组长,任中国科学院营养科学研究所学位委员会主任。主要学术兼职有:国际杂志Molecular Nutrition Food Research编委、美国癌症协会会员(American Association for Cancer Research, AACR)、国际CCN 基因族协会会员、中国营养协会会员。曾获美国南卡罗来纳州州立大学凯瑟琳遗传学奖、美国淋巴瘤基金会人才基金、上海市引进海外高层次留学人员专项资金、中国科学院“百人计划”、上海市“浦江人才计划”、国家“杰出青年科学基金”等多项奖励,目前主持承担国家863项目1项,973项目子项目1项,国家自然科学基金项目2项上海市基础研究重大项目子课题2项。在国际知名学术期刊上发表论文近30篇,指导博士研究生11名。
研究方向:肿瘤发生和发展的分子机制研究,主要针对在中国具有很高发病率及死亡率的肺癌、食管癌、胃癌、肝癌,还有虽然发病率不高但恶性程度却极高的大脑胶质细胞瘤。目前工作集中于CCN家族和Eph/ephrin家族分子在上述肿瘤中的作用机理和信号通路的研究。
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谢东, D
Leukemia (2000) 14, 805-810,-0001,():
-1年11月30日
Myelodysplastic syndromes (MDS) are a group of clonal hematologic disorders found predominantly in the elderly. The molecular mechanisms underlying the development of MDS remain obscure. In order to begin to identify tumor suppressor genes involved in these disorders, we performed a detailed microsatellite allelotype of chromosomal deletions associated with MDS. DNAs from both bone marrow and peripheral blood of 32 MDS patients were studied using 84 highly informative microsatellite markers on all autosomal arms, excluding the short arms of the acrocentric chromosomes. A high percentage of loss of heterozygosity (LOH) was identified on chromosome 5q (40% of informative cases), 7q (45%), 17p (23%) and 20q (20%), which corresponds to the most common cytogenetic abnormalities reported in MDS. In addition, a high incidence of LOH (>20%) was observed on chromosomal arms which had not been previously reported including 1p (36%), 1q (35%), and 18q (23%). This extensive allelotype analysis focuses attention on several novel genomic regions that probably contain novel tumor suppressor genes whose loss of function contributes to the development of MDS. Leukemia (2000) 14, 805–810.
MDS,
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谢东, Dong Xie, Carl W. Miller, James O’Kelly, Kei Nakachi, Akiko Sakashita, Jonathan W. Said, Jeffrey Gornbein, and H. Phillip Koeffler
The Journal of Biological Chemistry Vol. 276, No. 17, Issue of April 27, pp. 14187-14194, 2001,-0001,():
-1年11月30日
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谢东, Xiangjun Tong, Dong Xie, James O’Kelly, Carl W. Miller, Carsten Muller-Tidow, and H. Phillip Koeffler
The Journal of Biological Chemistry Vol. 276, No. 50, Issue of December 14, pp. 47709-47714, 2001,-0001,():
-1年11月30日
Cysteine-rich protein 61 (Cyr61) is a member of a family of growth factor-inducible immediate-early genes. It regulates cell adhesion, migration, proliferation, and differentiation and is involved in tumor growth. In our experiments, the role of Cyr61 in non-small cell lung cancer (NSCLC) was examined. Expression of Cyr61 mRNA was decreased markedly in four of five human lung tumor samples compared with their normal matched lung samples. NSCLC cell lines NCI-H520 and H460, which have no endogenous Cyr61, formed 60–90% fewer colonies after being transfected with a Cyr61 cDNA expression vector than cells transfected with the same amount of empty vector. After stable transfection of a Cyr61 cDNA expression vector, proliferation of both H520-Cyr61 and H460-Cyr61 sublines decreased remarkably compared with the cells stably transfected with empty vector. The addition of antibody against Cyr61 partially rescued the growth suppression of both H520-Cyr61 and H460-Cyr61 cells. Cell cycle analysis revealed that both H520-Cyr61 and H460-Cyr61 cells developed G1 arrest, prominently up-regulated expression of p53 and p21WAF1, and had decreased activity of cyclin-dependent kinase 2. The increase of pocket protein pRB2/p130 was also detected in these cells. Notably, both of the Cyr61-stably transfected lung cancer cell lines developed smaller tumors than those formed by the wild-type cells in nude mice. Taken together, we conclude that Cyr61 may play a role as a tumor suppressor in NSCLC.
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谢东, Dong Xie, , Dong Yin, Xiangjun Tong, James O’Kelly, Akio Mori, Carl Miller, Keith Black, Dorina Gui, Johathan W. Said, and H. Phillip Koeffler
CANCER RESEARCH 64, 1987-1996, March 15, 2004,-0001,():
-1年11月30日
Cyr61 is a member of the CCN family of growth factors; these proteins are secreted and can act as ligands of distinct integrins. We show that Cyr61 can enhance tumorigenicity of glioma cells acting through activated integrin-linked kinase (ILK) to stimulate β-catenin-TCF/Lef and Akt signaling pathways. Overexpression of Cyr61 occurred in highly tumorigenic glioma cell lines and in 68% of the most malignant glioblastoma multiforme brain tumors. Forced expression of Cyr61 in U343 glioma cells accelerated their growth in liquid culture, enhanced their anchorageindependent proliferation in soft agar, and significantly increased their ability to form large, vascularized tumors in nude mice. Overexpression of Cyr61 in the U343 cells led to the up-regulation of distinct integrins, including β1 and ανβ3, which have been shown to interact with Cyr61 and ILK. The activity of ILK was increased dramatically in these cells. Overexpression of Cyr61 also resulted in the phosphorylation of glycogen synthase kinase-3 and accumulation and nuclear translocation of -catenin, leading to activation of the -catenin-TCF/Lef-1 signaling pathway. Furthermore, forced expression of Cyr61 in the glioma cells activated phosphatidylinositol 3-kinase pathway, resulting in prominent phosphorylation of Akt and the antiapoptotic protein Bad. Cyr61 appears to stimulate several signaling pathways in the development of gliomas.
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谢东, Dong
Clinical Cancer Research Vol. 10, 2072-2801, March 15, 2004,-0001,():
-1年11月30日
The
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谢东, Xiangjun Tong, , James O’Kelly, Dong Xie, Akio Mori, Nathan Lemp, Robert McKenna, Carl W Miller and H Phillip Koeffler
Oncogene (2004) 23, 4847-4855,-0001,():
-1年11月30日
Cysteine-rich protein 61 (Cyr61) is a growth factorinducible, immediate-early gene that has multifaceted activities in various cancers. In a previous study, we found that Cyr61 inhibited the growth of the H520 and H460 non-small-cell lung cancer (NSCLC) cell lines.In further studies, we now report that p53 plays a pivotal role in Cyr61-dependent cellular growth arrest.Blockin g Cyr61 with a Cyr61 antibody resulted in the downregulation of expression of p53 and p21, as well as partially reversing the growth suppression of H520-Cyr61 cells. Proliferation of NSCLC cell lines (NCI-H157, H125, H1299), having a mutant p53, were not suppressed by Cyr61. Inhibition of wild-type p53, by either human papilloma virus type 16 E6 or a dominant-negative p53, resulted in the rescue of the growth suppression mediated by Cyr61 in the H520-Cyr61 cells. The enhanced levels of p21WAF1 and p130/RB2, in the Cyr61-expressing H520-Cyr61 cells, were also inhibited by blocking p53 showing that p21 and p130 were induced by p53 in these cells. In addition, levels of both c-myc and β-cateninincreased in Cyr61 stably transfected H520 Cells. Moreover, β-catenin was translocated into the nucleus in these cells. Inhibition of c-myc expression in the H520-Cyr61 cells with antisense c-myc resulted in their decreased levels of p53.Transf ecting cells with a dominant-negative T-cell factor (TCF4), the specific inhibitor of the β-catenin/TCF4 complex, downregulated the expression of c-myc. Take n together, the data suggest that Cyr61 suppressed the growth of NSCLC cells by triggering a signal transduction pathway through β-catenin. In this pathway, Cyr61 activated the β-catenin/TCF4 complex, which promoted the expression of c-myc and the latter induced expression of p53, and p53 upregulated p21WAF1 and p130/RB2, resulting in growth arrest.
Cyr61, β-catenin, c-myc, p53,, p21, p130
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谢东, Sigal
Clin Cancer Res 2005; 11 (20) October 15, 2005,-0001,():
-1年11月30日
Purpose: The connective tissue growth factor/cysteine-rich 61/nephroblastoma overexpressed (CCN) family consists of six matricellular proteins that are involved in various cellular functions, such as proliferation, development, and angiogenesis. The purpose of this study was to explore the possibility that CCN genes are involved in ovarian cancers. Experimental Design: We quantified CCN expression in a series of 59 ovarian cancers using quantitative real-time reverse transcription-PCR. CCN1 protein levels were further determined by immunohistochemistry and Western blot analysis. Overexpression and inhibition of CCN1 expression by small interfering RNA were used to examine its role in ovarian cancer cell proliferation in vitro and in vivo. Results: We found dysregulation of levels of the various CCN mRNAs in ovarian cancers compared with their expression in normal whole ovaries. Expression of CCN1 protein was detected in normal ovarian epithelial cells and ovarian tumors as well as in ovarian cancer cell lines. Furthermore, estrogen increased CCN1mRNA and protein levels in ovarian cancer cells. Ectopic expression of CCN1 enhanced the growth of ovarian cancer cells in liquid culture, whereas inhibition of its expression decreased proliferation and increased apoptosis in these cells. The observed changes in cell growth were accompanied with activation of Akt and extracellularsignal-regulated kinase (ERK) signaling pathways. Stable expression of CCN1 in SKOV3 cells significantly increased tumorigenicity in nude mice. Finally, overexpression of CCN1 conferred resistant to carboplatin-induced apoptosis in SKOV3 cells. Conclusions: This is the first study to show abnormalities in CCN expression in ovarian carcinomas. Furthermore, our results suggest that CCN1may play a role in ovarian carcinogenesis by stimulating survival and antiapoptotic signaling pathways.
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谢东, Jing-Jing
Biochemical and Biophysical Research Communictions 357 (2007) 648-654,-0001,():
-1年11月30日
During
Focal
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谢东, Yan
Caner Res 2007; 67 (6). March 15, 2007,-0001,():
-1年11月30日
IFN regulatory factor (IRF)-1 and IRF-2 are generally regarded as a tumor suppressor and an oncoprotein, respectively. However, little is known about their expression and function in esophageal squamous cell carcinomas (ESCC). In our present work, IRF-1 expression was decreased and IRF-2 expression was increased in ESCCs compared with matched normal esophageal tissues. Moreover, statistical data indicated that IRF-2 expression was tightly correlated with progression of ESCCs. As expected, overexpression of either IRF-1 or IRF-2 in an ESCC cell line resulted in either suppression or enhancement of cell growth, respectively. Also, proliferationand apoptosis-related molecules (p21WAF1/CIP1, cyclin-D1, Bcl-2, and histone H4) were regulated by IRF-1 and IRF-2. Additionally, high levels of IRF-2 blocked the function of IRF-1 by preventing the latter from translocating into the nucleus; in contrast, knock down of IRF-2 by small interfering RNA permitted nuclear localization and activity of IRF-1. In vivo assay using nude mice indicated that the tumorigenicity of ESCC cells was enhanced with IRF-2 overexpression but dramatically attenuated after forced expression of IRF-1. In conclusion, IRF-1 and IRF-2 are able to regulate tumorigenicity of ESCC cells as antioncoprotein and oncoprotein, respectively. Relative amounts of IRF-1 to IRF-2 are functionally very important for the development and progression of ESCCs, and reduction of the ratio of IRF-1/IRF-2 may lead to the enhancement of tumorigenicity of ESCC cells. Therefore, levels of IRF-1 and IRF-2 are useful indicators in diagnosis and prognosis for ESCCs, and these molecules are potential drug targets for ESCC therapy. [Cancer Res 2007;67(6):2535–43]
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