Mechanism of estrogen enhancement in the growth of androgen-dependent Shionogi carcinoma 115.
The mechanism of estrogen enhancement in the growth of androgen-dependent Shionogi carcinoma 115 (SC115) maintained in castrated DS mice by low doses of androgen (10 micrograms of testosterone propionate or 4 micrograms of 5 alpha-dihydrotestosterone/mouse/day) is reported. Although the low androgen treatment slightly but significantly (P less than 0.05) stimulated tumor growth, concomitant estrogen (4 micrograms of 17 beta-estradiol/mouse/day) significantly (P less than 0.01) enhanced the tumor growth. The high growth rate, histological type (medullary carcinoma), androgen dependency, and high androgen receptor content of the tumor grown during estrogen plus low androgen treatment did not differ significantly from those of the original SC115 tumor grown in normal males or in castrated mice treated with high doses of androgen. On the other hand, the treatment with low doses of androgen alone induced the development of slowly growing spindle-shaped cells from the medullary SC115 cells. The spindle-shaped cells containing low levels of androgen receptor were shown to be androgen independent and were also induced from the SC115 cells in nontreated castrated mice. These findings demonstrated that low doses of androgen and estrogen synergize to maintain and increase the growth of SC115 cells, whereas low doses of androgen alone fail to maintain the SC115 cells.
D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D002369:Castration; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000032:analysis / Q000473:pathology*; D051379:Mice; D008815:Mice, Inbred Strains; D009376:Neoplasms, Hormone-Dependent / Q000473:pathology*; D011944:Receptors, Androgen / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D013739:Testosterone / Q000378:metabolism / Q000494:pharmacology
D000728:Androgens; D004967:Estrogens; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D013739:Testosterone; D004958:Estradiol