Origin and progression of pregnancy-dependent mammary tumors induced by new mouse mammary tumor virus variants.
In order to study mechanisms of progression of mouse mammary tumor virus (MMTV)-induced pregnancy-dependent mammary lesions, we removed and serially transplanted 17 small tumors detected in MMTV-infected pregnant females. This gave rise to the same number of 'in vivo' tumor lines. Hormone-dependency of the passages was determined by comparing tumor development in multiparous versus virgin hosts. We found that the first passages of most of these lesions (11/17) required pregnancy to grow. However, all these tumor lines lost their hormone-dependence through successive passages. The original pregnancy-dependent lesions were mostly multiclonal and showed high levels of estrogen and progesterone receptors. Alternatively, pregnancy-independent tumors arose as clonal dominant populations exhibiting a lower hormone receptor content. Our data show that the progression of hormone-dependent MMTV-induced mammary tumors is an irreversible process associated with the appearance of additional MMTV insertional events as well as alterations in the composition of the tumor cell population.
D000818:Animals; D004273:DNA, Neoplasm / Q000378:metabolism; D018450:Disease Progression; D004967:Estrogens / Q000378:metabolism; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D008324:Mammary Tumor Virus, Mouse / Q000472:pathogenicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D009376:Neoplasms, Hormone-Dependent / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D011247:Pregnancy; D011270:Pregnancy, Animal; D011374:Progesterone / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism
D004273:DNA, Neoplasm; D004967:Estrogens; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D011374:Progesterone