Growth-stimulative effect of estrogen on androgen-dependent Shionogi carcinoma 115.
The stimulative effect of 17 beta-estradiol on the growth of androgen-dependent Shionogi carcinoma 115 and estrogen receptor in the tumor were studied. The incorporation of 17 beta-[3H]estradiol following a single injection of 17 beta-[3H]estradiol into tumor-bearing animals was 5- to 20-fold higher in the tumor than in the spleen and blood. Scatchard plot analyses showed that the tumor cytosol possessed a 17 beta-estradiol-binding site having a high affinity for 17 beta-estradiol [Kd 1.1 +/- 0.1 nM (S.E.)]. Competition experiments demonstrated that the 17 beta-estradiol binding was specific only for estrogenic compounds. Using sedimentation coefficient obtained by high-salt sucrose gradient (4.0S) and Stokes radius obtained by gel chromatography on Sephadex G-200 (46 A), the molecular weight of 17 beta-estradiol-binding component in the tumor cytosol was estimated to be 76,400. In castrated DS mice, a slight but significant increase in growth of s.c. grafted tumors was found by daily s.c. injections of either 17 beta-estradiol or 10 micrograms per mouse of testosterone propionate. Growth of the tumor maintained by 10 micrograms of testosterone propionate was augmented markedly by the addition of 4 micrograms of 17 beta-estradiol, and the growth approached the level induced by 100 micrograms of testosterone propionate. Simultaneous injections of bromocryptine inhibited an increase in 17 beta-estradiol-induced prolactin secretion but had no effect on the 17 beta-estradiol-enhanced tumor growth. These results demonstrate for the first time the stimulative effect of estrogen on the growth of androgen-dependent Shionogi carcinoma 115. The tumor contains typical estrogen receptor, which might be able to transmit estrogen signal to tumor cell nuclei with regard to tumor growth.
D000728:Androgens / Q000502:physiology*; D000818:Animals; D002369:Castration; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003600:Cytosol / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008815:Mice, Inbred Strains; D011944:Receptors, Androgen / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D013154:Spleen / Q000378:metabolism
D000728:Androgens; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D004958:Estradiol