From Normalcy to Neoplasia. The Role of Epithelial-Stromal Interactions in Regulating Mammary Growth and Differentiation

摘要

We identified molecules that are involved in the cross talk between the epithelial and mesenchymal components of the developing and involuting mammary gland. The EFGR protein was shown to mediate normal ductal morphogenesis by acting from the stromal cells on the development of the mammary epithelial ducts. Additional evidence was provided concerning the function of the Caspase 1 gene product during lobular-alveolar development and involution of the mammary gland after weaning. An interesting observation from this work was mammary epithelial cells that will succumb to apoptosis enter the cell cycle first. This observation implies that at least a subset of the redundant epithelial cells undergo activation before cell death. In preliminary work mammary glands from the MMP14 null mouse were shown to have less adipose tissue but ductal penetration of the fat pad and initial duct formation occurred by post-natal day 13. Further experimentation is required to determine if the reduction in adipose tissue is related - to the wasting phenotype of these animals, or is induced by the MMP14 null epithelial cells. The practical outcome of these studies is a better understanding of mammary gland development before, during and after pregnancy, and during the process of involution.