Divergent responses to epidermal growth factor in hormone sensitive and insensitive human prostate cancer cell lines

摘要

The present study was undertaken to compare the relationship between response to exogenous epidermal growth factor (EGF) and the expression of the EGF-receptor (EGF-R) in an androgen sensitive (LNCaP) and insensitive (DU145) prostate cancer cell line. Although both cell lines demonstrated a single EGF-R binding site of similar high affinities (mean dissociation constant (Kd) +/- S.D. for DU145 = 1.0 +/- 0.6 nmol l-1; LNCaP = 2.8 +/- 2.2 nmol l-1) the number of binding sites (RT) for the hormone insensitive DU145 cells (mean +/- S.D. = 2.5 +/- 1.0 x 10(5) sites/cell) and 10-fold greater than that expressed in the androgen responsive LNCaP cell line (mean +/- S.D. = 2.0 +/- 1 x 10(4) sites/cell). Additionally exogenous EGF only minimally affected the growth and DNA synthesis of DU145 cells whereas LNCaP cells showed a significant response which was dose dependent. The autologous production of EGF-like molecules by DU145 cells is believed to reduce the cells needs for exogenous mitogens, thereby rendering the cells autostimulatory. Treatment of LNCaP cells with Mibolerone--a synthetic androgen--did not affect either the expression of the EGF receptor or the proliferative response observed with EGF. Western blot analysis, using monoclonal antibodies directed against the EGF receptor revealed a band of approximately 170 kD with DU145 cell lysates but the LNCaP EGF receptor was not detected using this technique.