Ha-ras(Val12) oncogene increases susceptibility of NIH/3T3 cells to lovastatin

Meng Yao Chang, Ming Shiou Jan, Shen Jeu Won, Hsiao Sheng Liu

研究成果: Article同行評審

30 引文 斯高帕斯(Scopus)

摘要

This study demonstrates that Ha-ras(Val12) oncogene overexpression sensitizes NIH/3T3 fibroblasts to lovastatin (LOV) cytotoxicity. This sensitization is through apoptosis, which was characterized by increasing CPP32 (caspase-3) activity and DNA fragmentation. Bcl-2 overexpression increased the resistance of the Ha-ras transformants to LOV and rescued the cells from apoptosis, further confirming that the LOV-sensitive cells died of apoptosis. Further analysis showed that Ha-ras activity inversely correlated with WAF1 activity. LOV treatment suppressed Ha-ras activity but induced WAF1 activity and disrupted the cell population in G0/G1 and S phases. The Ha-ras transformants expressing either dominant negative Ras(Asn17) or Raf-1(CB4) showed reverted susceptibility to LOV. These data confirm the involvement of Ras and demonstrate that Raf-1 signalling is required for LOV-induced cell death. Taken together, the possible action of LOV-induced apoptosis is through suppressing Ha-ras activity and increasing WAF1 activity, which alters cell cycle progression and finally activates suppressed apoptotic pathway in a Fas/Fas-L- and p53-independent fashion.

原文English
頁(從 - 到)62-68
頁數7
期刊Biochemical and Biophysical Research Communications
248
發行號1
DOIs
出版狀態Published - 1998 7月 9

All Science Journal Classification (ASJC) codes

  • 生物物理學
  • 生物化學
  • 分子生物學
  • 細胞生物學

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