Trichostatin A inhibits beta-casein expression in mammary epithelial cells

Many aspects of cellular behavior are defined by the content of information provided by association of the extracellular matrix (ECM) and with cell me mbrane receptors. When cultured in the presence of laminin-containing ECM a nd prolactin (Prl), normal mammary epithelia] cells express the milk protei n beta -casein. We have previously found that the minimal ECM- and Prl-resp onsive enhancer element BCE-1 was only active when stably integrated into c hromatin, and that trichostatin A (TSA), a reagent that leads to alteration s in chromatin structure, was able to activate the integrated enhancer elem ent. We now show that endogenous beta -casein gene, which is controlled by a genetic assembly that is highly similar to that of BCE-1 and which is als o activated by incubation in ECM and Prl, is instead inhibited by TSA. We p rovide evidence that the differing response of beta -casein and BCE-1 to TS A is neither due to an unusual effect of TSA on mammary epithelia[ cells, n or 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 inves tigation, we also showed that ECM mediated rapid histone deacetylation in m ammary epithelial cells. These results are discussed in combination with pr evious work showing that TSA mediates the differentiation of many types of cancer cells but inhibits differentiation of some nonmalignant cell types. (C) 2001 Wiley-Liss, Inc.