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Suppression of Telomerase, Reexpression of KAI1, and Abrogation of Tumorigenicity by Nerve Growth Factor in Prostate Cancer Cell Lines¹

Division of Pharmacology, Department of Biomedical Sciences and Biotechnology, Brescia University Medical School, 25124 Brescia, Italy [S. S., D. B., C. M., P. F. S.]; Melanoma Center, Instituto Dermopatico dell’Immacolata, Via Monti di Creta 104, 00167 Rome, Italy [I. F., E. B.]; and Clinical Institut, Department of Endocrinology, Max Planck Institute of Psychiatry, D-80804 Munich, Germany [M. P-P.]

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 neurotrophin in the control of proliferation and progression of prostate cancers is still a matter of investigation.

Prostate adenocarcinomas are telomerase-positive tumors. Chronic exposure of DU145 and PC3 prostate tumor cell lines to NGF resulted in a dramatic down-regulation of telomerase activity. This effect was correlated in terms of concentrations and time with a remarkable down-regulation of cell proliferation both in vitro and in vivo but was not secondary to NGF-induced quiescence. No down-regulation of telomerase activity was, in fact, detectable during 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, which is present in the prostate and is progressively lost during the progression of prostate cancers. Chronic NGF treatment strongly induced the reexpression of this gene in these cell lines, and this effect was correlated with the suppression of their invasive potential in vitro. The data presented here suggest that NGF reverts two metastatic prostate cancer cell lines to slowly proliferating, noninvasive phenotypes characterized by a very low telomerase activity and by the expression of the KAI1 metastasis suppressor gene.

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