Stimulative effect of physiological doses of androgen or pharmacological doses of estrogen on growth of Shionogi carcinoma 115 in mice.
It was generally accepted for 20 yr that the growth of Shionogi carcinoma 115 (SC115) is stimulated only by androgen. In the present study, the growth-stimulative effect of estrogen alone on SC115 tumors was examined in castrated mice. Daily injections of physiological doses of 17 beta-estradiol did not enhance the tumor growth. However, high doses of 17 beta-estradiol (10-100 micrograms/mouse/day) significantly stimulated the growth of tumors in a dose-dependent manner. Since high doses of diethylstilbestrol (10-50 micrograms/mouse/day), which does not bind to androgen receptor, could markedly stimulate the growth of tumors and since antiandrogen (cyproterone acetate) failed to inhibit the growth stimulation induced by high doses of 17 beta-estradiol, it is concluded that high doses of 17 beta-estradiol, which binds to androgen receptor with relatively low but significant affinity, enhance the tumor growth not via the androgen receptor system. The growth speed, histological type, content, and affinity of androgen, estrogen, and progesterone receptors and pattern of newly synthesized proteins labeled in vitro with [35S]methionine of tumors grown by high doses of estrogen were not significantly different from those of the original SC115 tumors grown in normal males. Furthermore, seed tumors from one to six generations grown by pharmacological doses of estrogen alone could rapidly grow only in normal males and not in castrated males. The present findings demonstrate that the growth of SC115 tumors in vivo is stimulated by physiological doses of androgen or pharmacological doses of estrogen.
D000726:Androgen Antagonists / Q000494:pharmacology; D000728:Androgens / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004054:Diethylstilbestrol / Q000494:pharmacology; D004967:Estrogens / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000032:analysis / Q000473:pathology*; D051379:Mice; D008815:Mice, Inbred Strains; D009363:Neoplasm Proteins / Q000032:analysis; D009376:Neoplasms, Hormone-Dependent / Q000032:analysis / Q000473:pathology*; D011987:Receptors, Steroid / Q000032:analysis; D013739:Testosterone / Q000494:pharmacology
D000726:Androgen Antagonists; D000728:Androgens; D004967:Estrogens; D009363:Neoplasm Proteins; D011987:Receptors, Steroid; D013739:Testosterone; D004054:Diethylstilbestrol