Control of Uterine Epithelial Growth and Differentiation: Implications for Estrogen-Associated Neoplasia

Abstract

Estrogens have been associated with neoplasia in various target organs for many years. Since a consequence of estrogen administration is usually epithelial proliferation in these same target organs, the assumption underlying estrogen-associated neoplasia is that cell proliferation per se is the trigger for this condition. We have tested this assumption in nontarget cells in culture (Syrian hamster embryo cells, SHE cells) and have shown that various estrogens, both natural and synthetic, are capable of neoplastically transforming SHE cells in vitro in the absence of any enhanced cell proliferation (1). In fact, additional studies show that these cells lack most classical estrogen-growth responses and are relatively poor in ER (Tsutui et al., in preparation). Thus, at least in this in vitro system, cell transformation, the presence of classical ER, and enhanced growth response seem to be separable; however, congruence of ER and cell differentiation could not be determined since no differentiation-specific genes for estrogen action are yet known in this nontarget cell system. We decided, therefore, to study the role of cell proliferation and differentiation in a target tissue which, while relatively deficient in ER, provided marker genes for estrogen-associated cell differentiation. The tissue that met this criterion was the newborn mouse uterine epithelium.