Graduate Thesis Or Dissertation
 

Loss of rhythmic circadian clock gene expression is associated with decreases in estrogen receptor expression in canine mammary cancer

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https://ir.library.oregonstate.edu/concern/graduate_thesis_or_dissertations/zs25xc150

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  • The endogenous circadian clock is an intracellular transcriptional feedback loop timing daily patterns of multiple biological rhythms within a 24-hour period. Disturbance in various rhythms leads to alteration of normal biological processes including cellular proliferation and tumor suppression. Endogenous circadian clock rhythms have been found to be disrupted in breast cancer. These findings support the increasing evidence that circadian rhythm interference leads to an increased risk of breast cancer. Estrogens have also been found to play a role in breast cancer by acting on estrogen receptors (ER) to induce gene expression. Both human and canine mammary tumors have been found to express ER. Canine mammary cancer is known to be influenced by estrogen signaling, with early ovariectomy decreasing mammary cancer risk from 0.5 - 24%. There is also evidence of a link between ER and clock genes, which may be important in development of hormone related breast cancer. A canine mammary cancer cell line with ER expression has been established at the Oregon State University College of Veterinary Medicine and the purpose of this study was to use this in vitro model to investigate patterns of clock gene expression and ERα and ERβ. With increased cell passage we observed a loss of rhythmicity of expression of both clock genes Bmal1 and Per2 and esr1/2 (ERα/β). Additionally, preliminary results suggest that manipulation of ER expression may lead to resumption of clock gene rhythmicity. Furthermore, treatment with sirtinol, an inhibitor of the histone deacetylase (HDAC) class III Sirt1, indicated ERβ rhythmicity may be rescued by alteration of clock function via HDAC inhibition. Investigations of the relationship between ER and clock rhythmicity in this cell line are ongoing.
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file details HughesKellyL2014.pdf 2017-08-09 Público Baixar