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Trichostatin a inhibits β‐casein expression in mammary epithelial cells
Author(s) -
Pujuguet Philippe,
Radisky Derek,
Levy Dinah,
Lacza Charlemagne,
Bissell Mina J.
Publication year - 2001
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.1260
Subject(s) - trichostatin a , chromatin , microbiology and biotechnology , extracellular matrix , histone , enhancer , chemistry , cellular differentiation , gene expression , biology , gene , biochemistry , histone deacetylase
Many aspects of cellular behavior are defined by the content of information provided by association of the extracellular matrix (ECM) and with cell membrane receptors. When cultured in the presence of laminin‐containing ECM and prolactin (Prl), normal mammary epithelial cells express the milk protein β‐casein. We have previously found that the minimal ECM‐ and Prl‐responsive enhancer element BCE‐1 was only active when stably integrated into chromatin, and that trichostatin A (TSA), a reagent that leads to alterations in chromatin structure, was able to activate the integrated enhancer element. We now show that endogenous β‐casein gene, which is controlled by a genetic assembly that is highly similar to that of BCE‐1 and which is also activated by incubation in ECM and Prl, is instead inhibited by TSA. We provide evidence that the differing response of β‐casein and BCE‐1 to TSA is neither due to an unusual effect of TSA on mammary epithelial cells, nor to secondary consequences from the expression of a separate gene, nor to a particular property of the BCE‐1 construct. As a component of this investigation, we also showed that ECM mediated rapid histone deacetylation in mammary epithelial cells. These results are discussed in combination with previous work showing that TSA mediates the differentiation of many types of cancer cells but inhibits differentiation of some nonmalignant cell types. J. Cell. Biochem. 83: 660–670, 2001. © 2001 Wiley‐Liss, Inc.