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  • Title: Negative controls of cell proliferation: human prostate cancer cells and androgens.
    Author: Sonnenschein C, Olea N, Pasanen ME, Soto AM.
    Journal: Cancer Res; 1989 Jul 01; 49(13):3474-81. PubMed ID: 2731169.
    Abstract:
    LNCaP cells represent a useful tool to explore the mechanism of sex hormone action on cell proliferation in an "in culture-in animal" model. Results indicated that: (a) these cells were inhibited from proliferating for extended periods (up to 30 days) when placed in charcoal-dextran-stripped sera; they remained, however, viable because they proliferated when sex hormones were added to this medium; (b) the inhibitory effect of sera was reversed by the addition of 5 alpha-dihydrotestosterone at 3 x 10(-10) M, 17 beta-estradiol at 3 x 10(-8) M and higher concentrations, and progesterone at 3 x 10(-10) M and higher concentrations; (c) while the dose response to androgens was biphasic (i.e., 5 alpha-dihydrotestosterone at concentrations higher than 3 x 10(-10) M resulted in progressively lower cell yields), estrogens and progestagens exhibited a monophasic pattern; (d) these cells were exceedingly sensitive to the nutritional environment in which they grew; (e) while these cells have androgen receptors (68 fmol/mg protein; Kd = 2 x 10(-9) M), estrogen and progestagen receptors could not be detected by biochemical and immunocytochemical techniques; (f) tumors grew at the site of inoculation in castrated nude mice carrying 17 beta-estradiol and progesterone pellets and in intact male nude mice implanted with placebo pellets, while tumors did not grow in castrated nude mice implanted with a 5 alpha-dihydrotestosterone pellet. Taken together the data collected are compatible with the following conclusions: (a) the proliferative response in LNCaP cells seems not to be directly mediated by their intracellular androgen receptors; (b) plasma-borne trypsin-sensitive inhibitors of the proliferation of these cells (androcolyone I) appear to play a significant role in the proliferative event; (c) natural and synthetic androgens, estrogens, and progestagens cancelled the inhibition by charcoal-dextran-stripped human sera; (d) only androgens were able to trigger an inhibition of cell proliferation (shutoff effect) at concentrations higher than those that affected maximal cell yields (direct negative hypothesis); and (e) a faulty shutoff response is probably a crucial event for the tumorigenesis of these human prostate cells.
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