Function of PTP1B in Neuroendocrine Differentiation of Prostate Cancer
Annual rept. 1 Jan-31 Dec 2007
ROCHESTER UNIV NY
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The goal of the project is to identify the molecular mechanisms responsible for therapeutic failure in prostate cancer patients receiving hormonal therapy Scope The scope of the project is to use prostate cancer cell lines in in-vitro cell culture systems to study the complex signal transduction pathways that may be responsible for the neuroendocrine differentiation of prostate cancer cells, particularly the relationship of PTP1B to IL-8 signaling through its receptors CXCR1 and CXCR2, to IGF-1 receptor signaling through PI3 kinaseAKTmTOR pathway and to androgen receptor signaling. Major findings We have established LNCaP cell lines stably expressing CXCR1 and CXCR2. In such cell lines, PTP1B is overexpressed when compared with parental cells. There is also significant increase in the expression of NSE, a marker of neuroendocrine differentiation, in such stable cell lines. We studied the expression of IL-8 in LNCaP cells stably overexpressing PTP1B and a mutant PTP1B and found increased levels of IL-8 in such cell lines in comparison to parental LNCaP cells. Expression of IL-8 receptors CXCR1 and CXCR2 are also increased in these stable cell lines. A related but unexpected significant finding is that the neuroendocrine cells may be the stem cells of prostate cancer.
- Medicine and Medical Research