title: Androgenic and antiandrogenic control on epidermal growth factor, epidermal growth factor receptor, and androgen receptor expression in human prostate cancer cell line LNCaP.
abstract: 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.
authors.affiliation: Department of Experimental Medicine, University of L'Aquila, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Ravenna
authors.forename: C
authors.initials: C
authors.lastname: Lubrano
authors.forename: F
authors.initials: F
authors.lastname: Di Silverio
authors.forename: A
authors.initials: A
authors.lastname: Vacca
authors.forename: M P
authors.initials: MP
authors.lastname: Felli
authors.forename: M
authors.initials: M
authors.lastname: Maroder
authors.forename: G
authors.initials: G
authors.lastname: D'Eramo
authors.forename: F
authors.initials: F
authors.lastname: Sciarra
authors.forename: L
authors.initials: L
authors.lastname: Frati
authors.forename: A
authors.initials: A
authors.lastname: Gulino
mesh_terms: 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
chemical_list: D000726:Androgen Antagonists; D012333:RNA, Messenger; D011944:Receptors, Androgen; D015741:Metribolone; C014290:hydroxyflutamide; D004815:Epidermal Growth Factor; D005485:Flutamide; D066246:ErbB Receptors