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タイトル: Deregulated GSK3β sustains gastrointestinal cancer cells survival by modulating human telomerase reverse transcriptase and telomerase
著者: Mai, Wei
Kawakami, Kazuyuki link image
Shakoori, Abbas
Kyo, Satoru link image
Miyashita, Katsuyoshi
Yokoi, Kenji link image
Jin, Mingji
Shimasaki, Takeo
Motoo, Yoshiharu link image
Minamoto, Toshinari link image link image
川上, 和之
京, 哲
源, 利成
発行日: 2009年11月15日
出版社(者): American Association for Cancer Research
雑誌名: Clinical Cancer Research
ISSN: 1078-0432
巻: 15
号: 22
開始ページ: 6810
終了ページ: 6819
抄録: Purpose: Glycogen synthase kinase-3β (GSK3β) regulates multiple cell signaling pathways and has been implicated in glucose intolerance, neurodegenerative disorders, and inflammation. We investigated the expression, activity, and putative pathologic role of GSK3β in gastrointestinal, pancreatic, and liver cancers. Experimental Design: Colon, stomach, pancreatic, and liver cancer cell lines; nonneoplastic HEK293 cells; and matched pairs of normal and tumor tissues of stomach and colon cancer patients were examined for GSK3β expression and its phosphorylation at serine 9 (inactive form) and tyrosine 216 (active form) by Western immunoblotting and for GSK3β activity by in vitro kinase assay. The effects of small-molecule GSK3β inhibitors and of RNA interference on cell survival, proliferation, and apoptosis were examined in vitro and on human colon cancer cell xenografts in athymic mice. The effects of GSK3β inhibition on human telomerase reverse transcriptase (hTERT) expression and telomerase activity were compared between colon cancer and HEK293 cells. Results: Cancer cell lines and most cancer tissues showed increased GSK3β expression and increased tyrosine 216 phosphorylation and activity but decreased serine 9 phosphorylation compared with HEK293 cells and nonneoplastic tissues. Inhibition of GSK3β resulted in attenuated cell survival and proliferation and increased apoptosis in most cancer cell lines and in HT-29 xenografts in rodents but not in HEK293 cells. GSK3β inhibition in colon cancer cells was associated with decreased hTERT expression and telomerase activity. Conclusion: The results indicate that deregulated GSK3β sustains gastrointestinal cancer cells survival through modulation of hTERT and telomerase. © 2009 American Association for Cancer Research.
DOI: 10.1158/1078-0432.CCR-09-0973
URI: http://hdl.handle.net/2297/20398
資料種別: Journal Article
版表示: author
出現コレクション:1. 査読済論文

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