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Papers In Press, published online ahead of print October 11, 2001
Department of Hem/Oncology, Cedars-Sinai Medical Center, Los Angeles, CA 90048
Corresponding Author: xiangjuntong{at}hotmail.com
Cyr61 (Cysteine-rich protein 61) 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 markedly decreased in four of 5 human lung tumor samples compared to their normal matched lung samples. NSCLC cell lines NCI-H520 and H460, which have no endogenous Cyr61, formed 60-90% fewer colonies after 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 to 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 (CDK2). 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.
J. Biol. Chem, 10.1074/jbc.M107878200
Submitted on August 16, 2001
Revised on October 9, 2001
Accepted on October 10, 2001
Cyr61, a member of CCN family, is a tumor suppressor in non-small cell lung cancer
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