The role of Nerve Growth Factor (NGF), the low affinity p75Neurotrophin Receptor (NTR) and the high affinity Trk receptor in human prostate carcinogenesis

Nerve Growth Factor (NGF) is predominantly expressed by the stromal cells of the human prostate and stimulates growth of epithelia in a paracrine manner. During malignant transformation of the prostate, tumor cells acquire autocrine expression of NGF, thereby circumventing their paracrine dependence on stromal cell derived NGF. Epithelial expression of the p75 Neurotrophin Receptor (NTR) declines with malignant transformation of the prostate. Re-expression of the p75(NTR) by transfection of tumor cells reduces their rate of growth by increasing the rate of programmed cell death. Hence, the p75(NTR) appears to be a negative regulator of growth in prostate epithelia. Expression of the Trk receptor is retained during malignant transformation of prostate epithelia. NGF induces transphosphorylation of Trk, and its antagonism with K252a reduces the rate of growth of prostate tumor cells. Hence, the Trk receptor appears to positively regulate the NGF, stimulated cell growth of prostate tumors. Moreover a K252a analogue has been used, in clinical trials for the treatment of prostate cancer.