Session: SAT 292-325-Breast & Prostate Cancer
Poster Board SAT-300
Our results reveal the presence of circadian clock oscillations in our ER-positive tumor cells, a finding observed previously in human breast cancer cells. Circadian rhythms of ERα and ERβ expression were absent in these cells, however, suggesting that coupling of the clock mechanism to ER cycling is disrupted. Interestingly, treatment of canine tumor cells with sirtinol, an inhibitor of the histone deacetylase (HDAC) class III Sirt1, initiated circadian oscillations of ERβ (esr2) expression. Additionally, inhibition of class I HDACs with valproic acid resulted in a striking increase (but not rhythmicity) of ERβ, but not ERα, expression, demonstrating that chromatin remodeling mechanisms play a role in ER expression levels in mammary cancer. The observation of ERβ expression rhythms in the presence of Sirt1 inhibition suggests a clock control of ERβ abundance that may typically be disrupted in mammary cancer. A lack of proper temporal steroid hormone receptor-mediated activation and/or repression of multiple genes may represent one mechanism of tumor etiology or progression. Current studies are examining if resumption of ERβ rhythmicity via HDAC inhibition could result in alterations in proliferative rate of mammary tumors.
Nothing to Disclose: SB, KH, CPG, PEC
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