ANDROGENIC AND ANTIANDROGENIC CONTROL ON EPIDERMAL GROWTH-FACTOR, EPIDERMAL GROWTH-FACTOR RECEPTOR, AND ANDROGEN RECEPTOR EXPRESSION IN HUMAN PROSTATE-CANCER CELL-LINE LNCAP

Both androgen and antiandrogen treatments enhance the proliferation ra te of the hormone-dependent prostate cancer cell line LNCaP, expressin g a mutated androgen receptor (AR). We studied the modification of the expression of epidermal growth factor (EGF), of its receptor (EGF-R), and of androgen receptor (AR) in the LNCaP cell line, under basal con ditions and during androgen (R1881) and antiandrogen hydroxy-flutamide (OH-FLU) treatment. After prolonged R1881 administration, a marked in crease of EGF release was observed, completely blocked by the addition of OH-FLU. The Scatchard plot analysis of EGF-R binding revealed two classes of binding sites with high and low affinity. The administratio n of OH-FLU alone or combined with R1881 did not modify the affinity c onstants, while the low-affinity component disappeared after androgen administration. Both androgen and antiandrogen administration led to a significant increase of the EGF-R high-affinity component. AR mRNA an d protein levels were downregulated by R1881 treatment. Following OH-F LU administration, AR mRNA was slightly downregulated, and there was n ot a strict parallelism between AR mRNA levels and AR binding capacity . When combined with R1881, OH-FLU partially counteracted the androgen -induced AR downregulation. Our data show that EGFR binding capacity i s the only parameter constantly raised in cell. proliferation with res pect to quiescent cells, and highlights the nonunivocal action of OH-F LU on androgen-induced effects. (C) 1995 Wiley-Liss, Inc.