We hypothesize that Wnt signaling is important in maintaining the homeostasis of the prostate and in regulating the proliferation/differentiation of prostatic stem/progenitor cells. Molecular mechanisms important for modulating prostate stem cell activity after castration and regeneration are lacking. However there is evidence indicating that the Wnt signaling pathway can promote the regeneration of different tissues through self renewal of stem cells. Furthermore, deregulated Wnt signaling is implicated in tumor formation and correlates with a poor prognosis in prostate cancer. To understand the role Wnt signaling plays in prostate homeostasis, Wnt active cells will be isolated from the proximal/distal axis of prostatic ducts from transgenic mice. Using intact, castrated, and castrated and androgen supplemented animals we will determine how the Wnt signaling pathway relates to prostate involution and regeneration. In vitro and in vivo assays will be used to determine if the Wnt active cells isolated from transgenic mice have characteristics of stem cells. These experiments will define the role of the Wnt signaling pathway in the regulation of prostatic homeostasis as well as its function in the regulation of stem cell self-renewal and proliferation.
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