Down-regulation of Bcl-2-interacting protein BAG-1 confers resistance to anti-cancer drugs |
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Authors: | Takahashi Noriko Yanagihara Miyako Ogawa Yuzi Yamanoha Banri Andoh Toshiwo |
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Affiliation: | Department of Bioengineering, Faculty of Engineering, Soka University, Hachioji, Tokyo, Japan. |
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Abstract: | BAG-1 was originally identified as a binding partner of anti-apoptotic factor Bcl-2 [Takayama et al., Cell 80 (1995) 279-284]. Exogenous expression of BAG-1 was reported to confer cells resistance to several stresses [Chen et al., Oncogene 21 (2002) 7050]. We have obtained human cervical cancer HeLa cells with down-regulated BAG-1 levels by using a highly specific and efficient RNA interference approach. Surprisingly, cells with down-regulated BAG-1 exhibited significantly lower sensitivity against several anti-cancer drugs than parental cells expressing normal levels of the protein. Furthermore, growth rate of the cells was reduced when BAG-1 was down-regulated. Activity of ERK pathway appeared to be decreased in BAG-1 down-regulated cells, as shown by the reduced phosphorylation of ERK1/2 proteins. Taken together resistance against anti-cancer drugs acquired by BAG-1 down-regulated cells may well be accounted for by the retardation of cell cycle progression, implicating the importance of BAG-1 in cell growth regulation. |
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Keywords: | BAG-1 Bcl-2 Apoptosis RNA interference Anti-cancer drugs |
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