HORMONES AND MAMMARY CARCINOGENESIS IN MICE, RATS, AND HUMANS - A UNIFYING HYPOTHESIS

An attempt has been made to put forward a unifying hypothesis explaini ng the role hormones play in the genesis of mammary cancers of differe nt phenotypes and genotypes in mice, rats, and humans, Most mammary ca ncers in these species originate in luminal mammary epithelial cells l ining the mammary ducts and alveoli. These cancers are histopathologic ally diverse acid are classified on the basis of growth requirements a s hormone-dependent or hormone-independent tumors. In most strains of mice, mammary cancers at the time of detection are largely of the horm one-independent type; in rats, almost all mammary cancers are hormone- dependent, while humans have both phenotypes. In spite of these differ ences, in vivo studies show that hormones (ovarian and pituitary) are essential for luminal mammary epithelial cell proliferation and also f or the development of mammary cancers of both hormone-independent and hormone dependent types, This article, based on our extensive in vivo and in vitro studies and on current literature, proposes a model to ex plain the central role of hormones in the genesis of all types of mamm ary cancers. The model attempts to address the following questions: (i ) how hormones regulate luminal mammary epithelial cell proliferation, (ii) why hormones are required for the genesis of mammary cancers of all phenotypes and genotypes, including those which are always classif ied as hormone-independent tumors, and (iii) why the three species (mo use, rat, and human) have consistently different ratios of hormone-dep endent to hormone-independent tumors.