Estrogen receptor transcription and transactivation: Novel morphoregulatory functions for the adhesion receptor Ep-CAM in the mammary epithelium

Ep-CAM, an epithelial cell-cell adhesion receptor, is often over-expressed in association with proliferation and remodeling in epithelial tissues. Development of the mouse mammary gland during pregnancy is associated with a progressive upregulation of Ep-CAM expression, eventually reaching very high levels at day 16 of pregnancy. This phenomenon is paralleled by a concomitant branching of the mammary ductal tree and a sustained epithelial cell proliferation. Using a MMTV-LTR/Ep-CAM transgenic mouse model, we demonstrate that forced expression of Ep-CAM in the mammary epithelium leads to an induction of budding and secondary branching of the glandular tree in virgin females. Interestingly, a complete cycle of gestation in the Ep-CAM transgenic mice results in extreme ductal hyperplasia/ductectasia and lobular hypoplasia, in combination with partially decreased differentiation of both ductal and alveolar (lobular) epithelial cells. Surprisingly, mammary gland involution is affected because of a decreased frequency of apoptotic figures and increased rate of cell proliferation. These results support novel morphoregulatory functions for the adhesion receptor Ep-CAM in epithelial tissue development and homeostasis.