Somatostatin and the phosphorylation of the epidermal growth factor/transforming growth factor (TGF) receptor in LNCaP cells: interactions with a locally produced TGF

¹ Center for Endocrinological Oncology, Department of Endocrinology, Via G. Balzaretti 9, 20133 Milan, Italy

Somatostatin and its analogs have been shown to exert an antiproliferative action on different cell lines (Motta & Serio 1994, Cheung & Boyages 1995, Reubi & Laissue 1995, Yoshitomi et al. 1997). In particular, somatostatin has been demonstrated to inhibit directly the proliferation of the human prostatic cancer cell line, LNCaP (Lymph Node Carcinoma of the Prostate), and to induce a significant decrease in the proteins secreted by these cells (Brevini et al. 1993). The possibility of a functional link between the antiproliferative and the antisecretory actions of somatostatin has been suggested since, at least in LNCaP cells, both effects appear to involve tyrosine dephosphorylation processes (Brevini et al. 1993). Several growth stimulatory factors - epidermal growth factor (EGF), transforming growth factor alpha (TGFalpha), and basic fibroblast growth factor - are involved in the control of prostatic cancer growth (Schuurmans et al. 1991, Ching et al. 1993, Limonta et al. 1994), possibly acting via the intracellular activation of tyrosine kinases (Cooper & Hunter 1984, Gill 1990). Based on these observations, we have focussed our attention on the possibility that somatostatin might inhibit LNCaP cell growth by affecting phoshorylation processes connected with growth factor actions. Specifically, the interactions of somatostatin with the EGF/TGFalpha receptor family of tyrosine kinases have been considered. Moreover, the possibility that somatostatin might interfere with the release of ligands, possibly involved in an autocrine/paracrine activation of such a receptor has been investigated. To this purpose, the following experiments have been performed: (a) study of the possible interactions of somatostatin with the phosphorylation of the EGF/TGFalpha receptor in LNCaP cells; (b) analysis of the possible interactions of somatostatin with the activation of phosphotyrosine phosphatases; (c) evaluation of the interactions of somatostatin with the secretion of factors, such as TGFalpha, possibly acting as endogenous ligands for the EGF/TGFalpha receptor.

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Acknowledgements

This work was supported by AIRC, ACRO96.00594. PF 39 and by MURST.