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論文
論文
1. CTEN/tensin 4 expression induces sensitivity to paclitaxel in prostate cancer
Li, You Qiang ; Mizokami, Atsushi ; Izumi, Kouji ; Narimoto, Kazutaka ; Shima, Takashi ; Zhang, Jian ; Dai, Jinlu ; Keller, Evan T. ; Namiki, Mikio
出版情報: Prostate.  70  pp.48-60,  2010-01-01.  Wiley-Blackwell
URL: http://hdl.handle.net/2297/20335
概要: 金沢大学附属病院泌尿器科<br />BACKGROUND. Recently, we established paclitaxel-resistant prostate cancer cell lines (PC-3-TxR and DU1 … 45-TxR). To determine the mechanisms of paclitaxel resistance in PC-3-TxR cells, we compared the gene expression profiles between PC-3 and PC-3-TxR cells. Our results indicated that expression of the C-terminal tensin like protein (CTEN, tensin 4) gene was down-regulated by 10-fold in PC-3-TxR cells. We investigated the possibility that CTEN overexpression restores paclitaxel sensitivity. METHODS. We investigated how knockdown and overexpression of CTEN in androgen-independent cell lines affect paclitaxel sensitivity by colony formation assay and growth inhibition assay. To determine the mechanisms by which CTEN affects paclitaxel sensitivity, we investigated the relationships between CTEN and F-actin or epidermal growth factor receptor (EGFR) in PC-3 cells. We also examined the association between expression of CTEN and grade of prostate cancer by immunohistochemistry using tissue microarray analysis. RESULTS. Down-regulation of CTEN, which is located in the cytoskeleton, played an important role in paclitaxel resistance in PC-3-TxR cells. Knockdown of CTEN expression in PC-3 cells induced paclitaxel resistance. Overexpression of CTEN in PC-3-TxR and DU145-TxR cells restored paclitaxel sensitivity. CTEN expression was inversely correlated with F-actin and EGFR expression. Then knockdown of actin and EGFR in PC-3-TxR cells recovered paclitaxel sensitivity, indicating that CTEN down-regulation mediates paclitaxel resistance through elevation of EGFR and actin expression. Moreover, CTEN expression was inversely correlated with Gleason score. CONCLUSIONS. These results strongly suggested that CTEN plays an important role in paclitaxel sensitivity and that CTEN expression level may be a prognostic predictive factor for PCa patients. © 2009 Wiley-Liss, Inc. 続きを見る
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論文
論文
2. 前立腺癌再燃の分子機序解明とその治療戦略構築のための基礎的研究
並木, 幹夫 ; Namiki, Mikio
出版情報: 平成22(2010)年度 科学研究費補助金 基盤研究(B) 研究成果報告書 = 2010 Fiscal Year Final Research Report.  2008-2010  pp.5p.-,  2011-04-04. 
URL: http://hdl.handle.net/2297/00048965
概要: 1.前立腺癌の再燃に関与する因子として重要なものに副腎性アンドロゲンDHEAがあるが、これは、前立腺がん組織において癌細胞と間質細胞の協調的働きによりDHTに変換され、前立腺癌の再増殖に寄与することを証明した。2.前立腺癌の骨転移に関しては … 骨由来TGF-βの作用が重要で、抗アレルギー薬であるトラニラストが、その作用を抑制し、抗腫瘍効果をもたらす可能性があることを示した。3.再燃前立腺癌に対してはタキサン系抗癌剤を使用することが多いが、その薬剤に対する耐性メカニズムのひとつにCTENの発現低下が関与していることを証明した。<br />1. Adrenal androgen, DHEA, is important for recurrence of prostate cancer. Prostate cancer stromal cells and prostate cancer cells coordinately activate the androgen receptor through synthesis of T and DHT from DHEA. 2. Tranilast inhibits hormone refractory prostate cancer cell proliferation and suppresses TGF-β-associated osteoblastic changes. 3. We identified CTEN, one of important genes that is associated with paclitaxel resistance. Expression of CTEN recovered paclitacel-resistance.<br />研究課題/領域番号:2039042, 研究期間(年度):2008-2010<br />研究機関: 金沢大学医学系 続きを見る