Abstract:
:This study examined the mechanism for the anti-cancer effects of histone deacetylase (HDAC) inhibitor trichostatin A (TsA) in H-ras-transformed human breast epithelial (MCF10A-ras) cells. The effects of TsA on anti-cancer effects of MCF10A-ras cells were determined by measuring the level of cell cycle regulator expression and apoptotic cell death using Western blotting and flow cytometry analysis, respectively. TsA induced morphological changes, apoptotic cell death and modulation of the cell cycle regulatory proteins in the MCF10A-ras cells. TsA increased the levels of acetylated histone H3 and H4 in MCF10A-ras cells. In addition, TsA markedly down-regulated the expression of cyclin D1 and CDK4, up-regulated the expression of p21WAF1 and p53 and induced cell cycle arrest at the G1 phase in MCF10A-ras cells. The levels of hyperphosphorylation of the Rb protein were lower in MCF10A-ras cells after the TsA treatment. Furthermore, the up-regulation of p53 promoted Bax expression, which led to the activation of pro-caspase-3 and eventually to apoptosis in MCF10A-ras cells. TsA significantly increased the levels of ERK1/2 phosphorylation in MCF10A-ras cells. Overall, the TsA-activated ERK pathway plays an important role in cell cycle arrest and apoptosis through the ERK-dependent induction of p21 in Ras-related human cancer cells.
journal_name
Int J Mol Medjournal_title
International journal of molecular medicineauthors
Park H,Lee YJ,Kim TH,Lee J,Yoon S,Choi WS,Myung CS,Kim HSsubject
Has Abstractpub_date
2008-11-01 00:00:00pages
605-11issue
5eissn
1107-3756issn
1791-244Xjournal_volume
22pub_type
杂志文章abstract::The pathologic mechanisms of pulmonary fibrosis (PF), one of the most common chronic pulmonary diseases, remain unclear. Napsin A is an aspartic proteinase that has been regarded as a hallmark of pulmonary adenocarcinoma. The present study aimed to investigate the specific function and molecular mechanisms of Napsin A ...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
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journal_title:International journal of molecular medicine
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journal_title:International journal of molecular medicine
pub_type: 临床试验,杂志文章
doi:
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journal_title:International journal of molecular medicine
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