Study of Signal Transduction Pathway of TGF-b1 Induced Growth Arrest of NIH:OVCAR-3 Cell

• Main Authors: Huen-Juin Tzeng, 曾惠君
• Other Authors: Chin - Hsiang Chien
• Format: Others
• Language: zh-TW
• Published: 1999
• Online Access: http://ndltd.ncl.edu.tw/handle/51477606141263135573

碩士 === 國立陽明大學 === 生物化學研究所 === 87 === Abstract According to the previous studies, the growth of OVCAR-3 cell line was inhibited by the treatment of 5 ng/ml TGF-b1 and the cell cycle also arrested at G1 phase. PKC mediates the signal of growth arrest and induction of fos and jun expression in 15 min were found. In this study, the translocation of PKCa and PKCb from cytosol to cell membrane in five minutes was noticed; the result implied that PKCa and PKCb mediate TGF-b signaling in the early stage of treatment. TGF-b induction of Smad4 expression in OVCAR-3 cell was detected by Western blot analysis, whereas either Smad2 or Smad3 level was not changed by the same treatment. The TGF-b1 induced Smad4 protein accumulation could be blocked by 2 mM PMA as well as PKCa - specific protein kinase C inhibitor G?, but it could not be blocked by MEK-1 inhibitor PD098059. The results suggest that the signal of TGF-b1 induced Smad4 protein expression is mediated by PKC-dependent but not MAPK cascade-dependent pathway. The effects of TGF-b1 on the Cdk inhibitors p15, p21 and p27 were also detected; The expression of p21 increased whilst the level of p15 and p27 remain constant. If p21 transactivating the expression of Smad4 leading to the growth arrest of OVCAR-3 mainly through the PKC pathway by TGF-b treatment still needs to be investigated.