Background: Prostate cancer (PC) contains a minor component of neuroendocrine (NE) cells that may stimulate androgen-independent growth of the tumor. The mechanism of neuroendocrine differentiation remains unknown.
Methods: The expression of PTP1B, a protein tyrosine phosphatase, was studied in LNCaP cells induced to show neuroendocrine phenotype by androgen withdrawal. Wild-type PTP1B and its dominant-negative mutant were transfected into LNCaP cells to study their effects on neuroendocrine differentiation. In vivo expression of PTP1B in human prostate cancer was studied by immunohistochemistry.
Results: Androgen withdrawal of LNCaP cells led to increased expression of PTP1B with a corresponding increase in its tyrosine phosphatase activity. Overexpression of PTP1B in LNCaP cells led to neuroendocrine differentiation while expression of its dominant-negative mutant inhibited neuroendocrine differentiation. Immunohistochemical study showed that PTP1B was exclusively expressed in neuroendocrine cells of human prostate cancer tissue.
Conclusion: Our findings suggest that PTP1B plays an important role in neuroendocrine differentiation, and therefore, may possibly be involved in the progression of prostate cancer.
(c) 2006 Wiley-Liss, Inc.