Hormone-Dependent Mammary Tumors in Strain GR/A Mice. IV. Origin and Progression 2

Abstract
Two types of hormone-dependent mammary tumors that occur in strain GR/A mice, i.e., those that appear during pregnancy [pregnancy-dependent mammary tumors (PrDT)) and those induced by treatment with progesterone (P) and estrogen (E) [P+E-dependent mammary tumors (P+E-DT)), were compared in terms of serial transplantation, response to pregnancy, and histology. Both types originated as ductal hyperplasias. When the P+E-induced ductal hyperplasias were transplanted into the parenchyma-free mammary fat pad, they displayed behavior similar to that of pregnancy-induced tumors. P+E-induced ductal hyperplasias gave rise to ductal outgrowths in the virgin host and to PrDT in the pregnant host; this evidence indicated that the ductal hyperplasias are preneoplastic lesions in strain GR mice. In a separate study, attempts to induce progression of tumor occurrence toward pregnancy independence were made because no spontaneous progression had occurred after 8–9 serial transplant generations in PrDT lines. In contrast to nontransplanted PrDT, which usually require 3–5 forced breedings of mice to induce pregnancy independence, 6–8 matings were needed to induce progression to pregnancy independence in the transplanted lines. Results suggested that serial transplantation in the cleared fat pad may select for less neoplastic variants.