Development of androgen-stimulated transplants of Nb rat carcinoma of the dorsal prostate and their response to sex hormones and tamoxifen.

Androgen-stimulated tumors of the dorsal prostate were derived from an estrogen-dependent tumor of Nb rats (Nb-2Pr-E). The change followed repeated androgen treatments in a rat bearing a tumor which had regressed after estrogen removal. The eventual tumor regrowth provided tumor transplant lines, Nb-2Pr-A, which grew in normal or androgenized males, slowly in castrates, but not in estrogenized females. The Nb-2Pr-A growing tumors regressed after treatment with estrogen, and tumors which eventually regrew were autonomous. Slow tumor growth in castrated animals also responded to estrogen treatment. Tamoxifen, an antiestrogen, caused tumors growing in males to become stationary or regress. Regrowth of tumors after they had responded to tamoxifen again responded to castration or estrogen. Tumors which escaped from estrogen treatment or were autonomous did not respond to tamoxifen. The most effective sequence for treatment was tamoxifen followed by castration and, finally, estrogen. Tamoxifen treatment or castration allowed tumors to remain hormone responsive, whereas initial estrogen treatment prevented response to subsequent therapy and led to an autonomous change.