The Function of PTP1B in Neuroendocrine Differentation of Prostate Cancer
Annual rept. 1 Jan -31 Dec 2008
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 1. We have shown that IGF-1 receptor may be a critical player in androgen-withdrawal-induced neuroendocrine differentiation of prostate cancer cell line LNCaP. 2. We have shown that IGF-1 receptor is activated by the expression of a protein tyrosine phosphatase PTP1B in LNCaP cells, which may be responsible for the activation of AKT signaling pathway. In addition, our results suggest that this activity of PTP1B appears to be independent of its tyrosine phosphatase enzymatic activity.
- Medicine and Medical Research