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PMID: 11746508 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Trichostatin A inhibits beta-casein expression in mammary epithelial cells.

Journal of cellular biochemistry ·Vol. 83 ·No. 4 ·2001-00-00 ·Pages 660-70

Pujuguet P, Radisky D, Levy D, Lacza C, Bissell MJ

Abstract

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 beta-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 beta-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 beta-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.

MeSH Terms
Acetylation/drug effects Acetyltransferases/biosynthesis,genetics Animals Basement Membrane/chemistry Caseins/antagonists & inhibitors,biosynthesis,genetics,metabolism Cattle Cell Line Chromatin/drug effects,enzymology,metabolism Enhancer Elements, Genetic/drug effects Epithelial Cells/drug effects,metabolism Genes, Reporter/drug effects Histone Acetyltransferases Histones/metabolism Hydroxamic Acids/pharmacology Mammary Glands, Animal/cytology,drug effects,metabolism Membrane Proteins/antagonists & inhibitors,genetics,pharmacology Mice Protein Synthesis Inhibitors/pharmacology Recombinant Proteins/antagonists & inhibitors,pharmacology Saccharomyces cerevisiae Proteins Transcription, Genetic/drug effects Transcriptional Activation/drug effects
Chemicals
Caseins Chromatin Histones Hydroxamic Acids Membrane Proteins Protein Synthesis Inhibitors Recombinant Proteins Saccharomyces cerevisiae Proteins trichostatin A Acetyltransferases Histone Acetyltransferases
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Pujuguet P
Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.
Radisky D
Levy D
Lacza C
Bissell M J
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Article Info
Journal
Journal of cellular biochemistry
Abbr.
J Cell Biochem
ISSN
0730-2312
DOI
10.1002/jcb.1260
Published
2001-00-00
Pages
660-70
Language
English
Region
United States
NLM ID
8205768
PMCID
PMC2949289
Subset
IM
Grants
NCI NIH HHS · R01 CA057621 · United States
NCI NIH HHS · R01 CA057621-11 · United States
NCI NIH HHS · CA-57621-02 · United States
External Links
PubMed source DOI: 10.1002/jcb.1260 PMC Full Text View journal details
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