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 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.
Pujuguet
P
P
Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.
Radisky
D
D
Levy
D
D
Lacza
C
C
Bissell
M J
MJ
D000107:Acetylation / Q000187:drug effects; D000123:Acetyltransferases / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D001485:Basement Membrane / Q000737:chemistry; D002364:Caseins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D002417:Cattle; D002460:Cell Line; D002843:Chromatin / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D004742:Enhancer Elements, Genetic / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism*; D017930:Genes, Reporter / Q000187:drug effects; D051548:Histone Acetyltransferases; D006657:Histones / Q000378:metabolism; D006877:Hydroxamic Acids / Q000494:pharmacology*; D008321:Mammary Glands, Animal / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000494:pharmacology; D051379:Mice; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000494:pharmacology; D029701:Saccharomyces cerevisiae Proteins; D014158:Transcription, Genetic / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects
D002364:Caseins; D002843:Chromatin; D006657:Histones; D006877:Hydroxamic Acids; D008565:Membrane Proteins; D011500:Protein Synthesis Inhibitors; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; C012589:trichostatin A; D000123:Acetyltransferases; D051548:Histone Acetyltransferases