Suppression of telomerase, reexpression of KAI1, and abrogation of tumorigenicity by nerve growth factor in prostate cancer cell lines

Nerve growth factor (NGF) is expressed in the prostate, where it appears to be involved in the control of epithelial cell growth and differentiation. NGF production is decreased in prostate tumors. However, the role of this n eurotrophin in the control of proliferation and progression of prostate can cers is still a matter of investigation. Prostate adenocarcinomas are telomerase-positive tumors. Chronic exposure o f DU145 and PC3 prostate tumor cell lines to NGF resulted in a dramatic dow n-regulation of telomerase activity. This effect was correlated in terms of concentrations and time with a remarkable down-regulation of cell prolifer ation both in vitro and in vivo but was not secondary to NGF-induced quiesc ence. No down-regulation of telomerase activity was, in fact, detectable du ring serum starvation-induced quiescence. LNCaP cells, which do not express NGF receptors, appear to be insensitive to the actions of NGF. DU145 and PC3 cells do not express the KAI1 metastasis suppressor gene, whi ch is present in the prostate and is progressively lost during the progress ion of prostate cancers. Chronic NGF treatment strongly induced the reexpre ssion of this gene in these cell lines, and this effect was correlated with the suppression of their invasive potential in vitro. The data presented h ere suggest that NGF reverts two metastatic prostate cancer cell lines to s lowly proliferating, noninvasive phenotypes characterized by a very low tel omerase activity and by the expression of the KAI1 metastasis suppressor ge ne.