Maintenance of androgen-, glucocorticoid- or estrogen-responsive growth in shionogi carcinoma 115 subline sustained in castrated mice with high dose of estrogen for 30 generations (3 years).

Shionogi carcinoma 115 (SC115), an androgen-dependent mouse mammary tumor, rapidly loses its androgen responsiveness after androgen withdrawal. The growth of this tumor can also be stimulated by high doses of estrogen or glucocorticoid. In the present study, the maintenance of hormone-responsive growth of SC115 tumors with a high dose of estrogen was examined in castrated male mice using an SC115 subline obtained by serial transplantations of SC115 tumors in estrogen-treated castrated mice for 3 years (30 generations) (subline E2). Seed tumors from both SC115 and subline E2 could rapidly grow in castrated mice given daily injections of testosterone propionate (TP), 17 beta-estradiol (E2), or dexamethasone (Dex) (100 micrograms/mouse/day) but not in those given vehicle alone. Although SC115 and subline-E2 tumors grown with TP or Dex showed temporary regression after steroid withdrawal, the tumors grown with E2 did not show such temporary regression. The TP-, E2-, or Dex-induced growth of subline-E2 tumors was almost the same as that of the original SC115 tumors. However, responsiveness to androgen, estrogen or glucocorticoid of both tumors disappeared within one passage in steroid-depleted castrated mice. The present findings demonstrate that the loss of responsiveness to androgen as well as to high doses of estrogen or glucocorticoid of SC115 tumors can be prevented in castrated mice not only with androgen but also with high doses of estrogen.

Shionogi carcinoma 115

SCI 15 subline obtained by serial transplantations of SCI 15 tumors in E2 (high dose, 100μg/mouse/day)‐treated castrated mice for 3 years (30 generations)

androgen receptor

estrogen receptor

glucocorticoid receptor

testosterone propionate

17β‐estradiol

dexamethasone

mouse mammary tumor virus

long terminal repeat

fibroblast growth factor