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 rate of the hormone-dependent prostate cancer cell line LNCaP, expressing 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 conditions and during androgen (R1881) and antiandrogen hydroxy-flutamide (OH-FLU) treatment. After prolonged R1881 administration, a marked increase 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 administration of OH-FLU alone or combined with R1881 did not modify the affinity constants, 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 and protein levels were downregulated by R1881 treatment. Following OH-FLU administration, AR mRNA was slightly downregulated, and there was not 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 EGF-R binding capacity is the only parameter constantly raised in cell proliferation with respect to quiescent cells, and highlights the nonunivocal action of OH-FLU on androgen-induced effects.
Ravenna
L
L
Department of Experimental Medicine, University of L'Aquila, Italy.
Lubrano
C
C
Di Silverio
F
F
Vacca
A
A
Felli
M P
MP
Maroder
M
M
D'Eramo
G
G
Sciarra
F
F
Frati
L
L
Gulino
A
A
D000726:Androgen Antagonists / Q000494:pharmacology; D015152:Blotting, Northern; D015536:Down-Regulation / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000096:biosynthesis* / Q000187:drug effects; D066246:ErbB Receptors / Q000096:biosynthesis* / Q000187:drug effects; D005485:Flutamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008297:Male; D015741:Metribolone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000378:metabolism*; D011485:Protein Binding; D012333:RNA, Messenger / Q000032:analysis; D011863:Radioimmunoassay; D011944:Receptors, Androgen / Q000096:biosynthesis* / Q000187:drug effects; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000726:Androgen Antagonists; D012333:RNA, Messenger; D011944:Receptors, Androgen; D015741:Metribolone; C014290:hydroxyflutamide; D004815:Epidermal Growth Factor; D005485:Flutamide; D066246:ErbB Receptors