Interaction of IGF-binding protein-related protein 1 with a novel protein, neuroendocrine differentiation factor, results in neuroendocrine differentiation of prostate cancer cells

Neuroendocrine cells have been implicated in many cancers, including small cell lung, cervical, breast, and prostate carcinomas. The increase in neuroendocrine cell number in prostate cancer has been reported to correlate with poor prognosis, progressive tumors, and androgen insensitivity. The mechanisms involved in this differentiation remain unknown. IGF-binding protein-related protein 1 is a member of the IGF-binding protein superfamily and has recently been shown to exhibit differentiation and tumor suppression activity in prostate cancer cell lines stably overexpressing IGF-binding protein-related protein 1. From a yeast two-hybrid screen, a novel IGF-binding protein-related protein 1-interacting protein was identified. Immunocytochemical techniques indicate that this protein, 25.1, and intracellular IGF-binding protein-related protein 1 colocalize in the nucleus. When 25.1 is transiently expressed in a stable prostate cancer cell line overexpressing IGF-binding protein-related protein 1, cells assume a neuritic-like morphology with long dendritic-like processes and express the neuroendocrine markers chromogranin A and neuron-specific enolase. We propose that 25.1 (neuroendocrine differentiation factor) together with IGF-binding protein-related protein 1 can induce neuroendocrine cell differentiation in prostate cancer cells.