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 neuro endocrine cell number in prostate cancer has been reported to correlate wit h poor prognosis, progressive tumors, and androgen insensitivity. The mecha nisms involved in this differentiation remain unknown. IGF-binding protein- related protein 1 is a member of the IGF-binding protein superfamily and ha s recently been shown to exhibit differentiation and tumor suppression acti vity in prostate cancer cell lines stably overexpressing IGF-binding protei n-related protein 1. From a yeast two-hybrid screen, a novel IGF-binding pr otein-related protein 1-interacting protein was identified. Immunocytochemi cal techniques indicate that this protein, 25.1, and intracellular IGF-bind ing protein-related protein 1 colocalize in the nucleus. When 25.1 is trans iently expressed in a stable prostate cancer cell line overexpressing IGF-b inding protein-related protein 1, cells assume a neuritic-like morphology w ith long dendritic-like processes and express the neuroendocrine markers ch romogranin A and neuron-specific enolase. We propose that 25.1 (neuroendocr ine differentiation factor) together with IGF-binding protein-related prote in 1 can induce neuroendocrine cell differentiation in prostate cancer cell s.