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标题：Adenovirus-directed expression of Q227L-Gαs inhibits growth of established tumors of later-stage human breast cancer cells in athymic mice
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作者：Tara Ann Santore ; Yibang Chen ; Martine J. Smit 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2002
卷号：99
期号：3
页码：1671-1676
DOI：10.1073/pnas.032661999
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Elevation of cAMP inhibits proliferation and expression of the transformed phenotype in several cell types. We studied the effects of elevation of cAMP and expression of mutant (Q227L) activated Gs on the proliferation and tumorigenic capability of the later stage, metastatic estrogen-independent human breast cancer cell lines MDA-231 and MDA-435. Our studies show that 8Br-cAMP inhibits proliferation of these cells in culture and their ability to form colonies in soft agar. This inhibition may occur by different mechanisms in the two cell types. In MDA-231 cells, cAMP elevation results in sustained expression of the cell cycle inhibitor p27kip1 and inhibition of CDK2 activity, whereas in MDA-435 cells inhibition of mitogen-activated protein (MAP) kinase 1,2 activity is observed. We tested whether these effects in culture could be translated into inhibition of tumor growth in vivo. Tumors were developed in athymic (Nu/Nu) mice by injections of MDA-231 or MDA-435 cells. Injection of Q227L-Gs expressing adenoviral vector into these established tumors inhibited further tumor growth under conditions where tumors injected with either saline or adenoviral vector containing {beta}-galactosidase grew up to four to five times their original size. These results raise the possibility that sustained elevation of cAMP may have therapeutic value in the treatment of estrogen-resistant later stage breast cancers.
关键词：signaling pathway interactions‖cAMP‖MAP kinase‖inhibition of tumor growth