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Overexpression of BAD preferentially augments anoikis
Author(s) -
Idogawa Masashi,
Adachi Masaaki,
Minami Takae,
Yasui Hiroshi,
Imai Kohzoh
Publication year - 2003
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.11399
Subject(s) - anoikis , transfection , apoptosis , phosphorylation , phosphatase , protein kinase b , microbiology and biotechnology , biology , serine , kinase , cancer research , chemistry , gene , programmed cell death , biochemistry
BAD is a BH3‐only protein, and its proapoptotic activity is negatively regulated by serine phosphorylation. Here, we show that overexpression of BAD preferentially augments anchorage loss–induced apoptosis (anoikis). Gene transfer–mediated BAD overexpression alone did not induce apoptosis in attached MDCK cells but strongly augmented apoptosis when cells were cultured in suspension. In contrast, overexpression of another BH3‐only protein, BID, displayed much lower augmentation of anoikis, suggesting a preferential contribution of BAD to anoikis. During suspension culture, unphosphorylated BAD was gradually increased and targeted to the mitochondria. Cotransfection of BAD with constitutively active Akt cDNA strongly inhibited this change. In contrast, the increase of unphosphorylated BAD was not significantly inhibited by several phosphatase inhibitors or cotransfection with a dominant negative calcineurin cDNA, implying that the increase may be mainly due to a decrease of serine kinase activity, such as that of Akt. Similar results were observed in COS‐7 cells, suggesting that BAD overexpression can increase sensitivity of anchorage‐dependent cancer cells to anoikis. Thus, we propose that BAD can serve as a valuable gene therapeutic molecule to inhibit carcinoma progression. © 2003 Wiley‐Liss, Inc.

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