MS-275, a histone deacetylase inhibitor, selectively induces transforming growth factor β type II receptor expression in human breast cancer cells

BI Lee, SH Park, JW Kim, EA Sausville, HT Kim… - Cancer research, 2001 - AACR
BI Lee, SH Park, JW Kim, EA Sausville, HT Kim, O Nakanishi, JB Trepel, SJ Kim
Cancer research, 2001AACR
Transcriptional repression of the transforming growth factor (TGF)-βtype II receptor (Tβ RII)
gene appears to be a major mechanism to inactivate TGF-β responsiveness in many human
cancers. Because histone acetylation/deacetylation plays a role in transcriptional regulation,
we have examined the effect of MS-275, a synthetic inhibitor of histone deacetylase, in
human breast cancer cell lines. MS-275 showed antiproliferative activity against all human
breast cancer cell lines examined and induced TβRII mRNA, but not TGF-β type I receptor …
Abstract
Transcriptional repression of the transforming growth factor (TGF)-βtype II receptor (RII) gene appears to be a major mechanism to inactivate TGF-β responsiveness in many human cancers. Because histone acetylation/deacetylation plays a role in transcriptional regulation, we have examined the effect of MS-275, a synthetic inhibitor of histone deacetylase, in human breast cancer cell lines. MS-275 showed antiproliferative activity against all human breast cancer cell lines examined and induced TβRII mRNA, but not TGF-β type I receptor mRNA. MS-275 caused an accumulation of acetylated histones H3 and H4 in total cellular chromatin. An increase in the accumulation of acetylated histones H3 and H4 was detected in the TβRII promoter after treatment with MS-275. However, the level of histone acetylation did not change in chromatin associated with the TGF-β type I receptor gene. MS-275 treatment enhanced TGF-β1-induced plasminogen activator inhibitor 1 expression. Thus,antitumor activity of MS-275 may be mediated in part through the induction of TβRII expression and consequent potentiation of TGF-β signaling.
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