Inhibition of hamster melanoma growth by estrogen.
A malignant hamster melanoma cell line HM-1 derived from the heterogenous malignant hamster melanoma MM1 contains a specific, high affinity binding protein for estrogens. Partial purification of the binding protein with ammonium sulfate (40% saturation) increased mean binding content (3.1 +/- 1.2 (SD) fmol/mg protein) 15-fold without any change in affinity (10(10) M-1). The binding protein sedimented at 8-9S on 10-30% low salt sucrose gradients and 9-10S in the presence of 20 mM molybdate ion. Addition of 0.4 M KCl shifted the 8S peak to 4S. Binding was specific, saturable, and indicative of a single class of high affinity sites over a concentration range of 0.01-10.0 nM [3H]estradiol. Estradiol produced a dose related inhibition of HM-1 growth in vitro without altering the growth of an additional line (HM-2) which did not bind estrogen. The antiestrogen tamoxifen (10(-7) M) also significantly inhibited HM-1 melanoma growth in vitro, which was reversed by the addition of estradiol (10(-9) M). HM-1 xenografts grew faster in female BALB/c-nu/nu mice than male mice while there was no sex difference in HM-2 growth. Pharmacological doses of estradiol and the antiestrogen nafoxidine significantly inhibited HM-1 growth without altering tumor incidence or latency. Our observations suggest that HM-1 cell lines bind estrogens specifically and with high affinity and that hamster melanoma cells positive for this binding protein respond to estrogen.
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D006224:Cricetinae; D003600:Cytosol / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D008297:Male; D008546:Melanoma, Experimental / Q000473:pathology* / Q000503:physiopathology; D051379:Mice; D008819:Mice, Nude; D014442:Monophenol Monooxygenase / Q000378:metabolism; D009256:Nafoxidine / Q000494:pharmacology; D011960:Receptors, Estrogen / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology
D011960:Receptors, Estrogen; D013629:Tamoxifen; D009256:Nafoxidine; D004958:Estradiol; D014442:Monophenol Monooxygenase