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Stimulatory heterotrimeric GTP-binding protein augments cisplatin-induced apoptosis by upregulating Bak expression in human lung cancer cells

Cited 6 time in Web of Science Cited 6 time in Scopus
Authors
Choi, Yoon Jung; Oh, Jung-Min; Kim, So-Young; Seo, Miran; Juhnn, Yong-Sung
Issue Date
2009-06
Publisher
WILEY-BLACKWELL PUBLISHING, INC
Citation
CANCER SCIENCE; Vol.100 6; 1069-1074
Abstract
The present study aimed to investigate the effect of the stimulatory heterotrimeric GTP-binding (Gs) protein signaling system on cisplatin-induced apoptosis of lung cancer cells and its underlying mechanism as an attempt to develop a novel strategy to improve the therapeutic efficacy of cisplatin. Overexpression of the constitutively active alpha subunit of Gs (G alpha sQL) in A549 human lung cancer cells increased cisplatin-induced apoptosis, and knockdown of G alpha s with small hairpin RNA decreased the percentage of apoptotic cells. G alpha sQL increased the expression of the proapoptotic proteins B-cell leukemia/lymphoma-2 genes (Bcl-2) homologous antagonist killer protein (Bak) and Bcl-2 associated X protein (Bax), and decreased the expression of the antiapoptotic proteins Bcl-2 and Bcl-Xlong protein. Knockdown of Bak blocked the augmentative effects of G alpha sQL. G alpha sQL decreased the degradation rate of the Bak protein, and increased Bak mRNA transcript levels. G alpha sQL increased Bak-luciferase activity in a protein kinase A and cyclic AMP response element-dependent manner. G alpha sQL also augmented cisplatin-induced apoptosis of H1299 human lung cancer cells that lack functional p53. From this study, it is concluded that G alpha s augments cisplatin-induced apoptosis of lung cancer cells partially through upregulating Bak expression by increasing transcription and by decreasing the rate of protein degradation. (Cancer Sci 2009; 100: 1069-1074).
ISSN
1347-9032
Language
English
URI
http://hdl.handle.net/10371/76854
DOI
https://doi.org/10.1111/j.1349-7006.2009.01136.x
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College of Medicine/School of Medicine (의과대학/대학원)Dept. of Biochemistry & Molecular Biology (생화학교실)Journal Papers (저널논문_생화학교실)
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