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ID 8405
Eprint ID
8405
フルテキストURL
Thumnail K003007.pdf 102 KB
タイトル(別表記)
15-デオキシ-12,14-プロスタグランジンJ2による軟骨肉腫細胞の成長抑制機序におけるBax/Bcl-xLとp21発現変化
著者
申 正男 岡山大学
抄録
We previously reported that 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)), the most potent agonist for peroxisome proliferator-activated receptor gamma (PPAR gamma), induces apoptosis of human chondrosarcoma cell line OUMS-27. The current study aimed to explore the mechanism of 15d-PGJ(2)-induced apoptosis and inhibition of cell proliferation in OUMS-27 cells. The preliminary results of cDNA microarray analysis showed the down-regulation of anti-apoptotic Bcl-xL and up-regulation of pro-apoptotic Bax in the process of 15d-PGJ(2)-induced apoptosis. These changes were further confirmed at mRNA and protein levels by RT-PCR and Western blot analysis, respectively. Among cyclin-dependent kinase inhibitors, p21 was induced and up-regulated by 15d-PGJ(2), but p16 and p27 were not changed, suggesting that the involvement of p21 in inhibition of cell proliferation. Activation of caspase-3 by 15d-PGJ(2) was partly, but not completely, blocked by PPAR gamma antagonist (GW9662) suggesting the 15d-PGJ(2) exerted its effect by PPAR gamma-dependent and -independent pathways. Interestingly, immunohistochemical study on human chondrosarcoma samples revealed that Bcl-xL is frequently expressed by tumor cells. The results of the current study suggest that the potential ability of 15d-PGJ(2) in regulation of cell cycle and inhibition of Bcl-xL expression might be beneficial in the development of novel pharmacological agents for chondrosarcoma.
キーワード
Chondrosarcoma
Apoptosis
PPARγ
15d-PGJ2
Bcl-xL
p21
備考
http://dx.doi.org/10.1016/j.bbrc.2004.12.186
発行日
2005-06-30
出版物タイトル
資料タイプ
学位論文
学位授与番号
甲第3007号
学位授与年月日
2005-06-30
学位・専攻分野
博士(医学)
授与大学
岡山大学
オフィシャル URL
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15694358&dopt=Abstract
言語
Japanese
論文のバージョン
none
査読
不明