Histone deacetylase inhibition and estrogen signalling in human breast cancer cells.
Estrogens are steroid hormones, which act through specific nuclear estrogen receptors (ERalpha and ERbeta) and are important regulators of breast cancer growth. These receptors control gene expression by recruiting transcriptional cofactors that exhibit various enzymatic activities such as histone acetyltransferase or histone deacetylase (HDAC) which target histone as well as non-histone substrates. The ERalpha itself and some of the transcriptional regulators have been shown to be acetylated proteins. Research performed over the last decade has highlighted the role of HDAC inhibitors (HDACi) as modulators of transcriptional activity and as a new class of therapeutic agents. In human cancer cells, inhibition of HDACs controls the expression of the ERalpha gene and the transcriptional activity in response to partial antiestrogens such as 4-hydroxytamoxifen. Various HDACi strongly inhibit breast cancer cell proliferation and ERalpha-negative (ER-) appear less sensitive than ERalpha-positive (ER+) cell lines. p21WAF1/CIP1 gene expression, in relation with ERalpha levels, could play a role in this differential response of breast cancer cells to hyperacetylating agents.
INSERM U540 Endocrinologie Moléculaire et Cellulaire des Cancers and Université de Montpellier I, 60 Rue de Navacelles, 34090, France.
Raphaël
R
Margueron
Vanessa
V
Duong
Audrey
A
Castet
Vincent
V
Cavaillès
D000107:Acetylation / Q000187:drug effects; D001943:Breast Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D020847:Estrogen Receptor Modulators / Q000494:pharmacology; D047628:Estrogen Receptor alpha; D004967:Estrogens / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014407:Tumor Cells, Cultured
D004791:Enzyme Inhibitors; D020847:Estrogen Receptor Modulators; D047628:Estrogen Receptor alpha; D004967:Estrogens; D056572:Histone Deacetylase Inhibitors; D011960:Receptors, Estrogen