Abstract
During normal postnatal mammary gland development and adult remodeling related to the menstrual cycle, pregnancy, and lactation, ovarian hormones and peptide growth factors contribute to the delineation of a definite epithelial cell identity. This identity is maintained during cell replication in a heritable but DNA-independent manner. The preservation of cell identity is fundamental, especially when cells must undergo changes in response to intrinsic and extrinsic signals. The maintenance proteins, which are required for cell identity preservation, act epigenetically by regulating gene expression through DNA methylation, histone modification, and chromatin remodeling. Among the maintenance proteins, the Trithorax (TrxG) and Polycomb (PcG) group proteins are the best characterized. In this review, we summarize the structures and activities of the TrxG and PcG complexes and describe their pivotal roles in nuclear estrogen receptor activity. In addition, we provide evidence that perturbations in these epigenetic regulators are involved in disrupting epithelial cell identity, mammary gland remodeling, and breast cancer initiation.
Highlights
Estrogen and the Mammary GlandThe development of the mammary gland, unlike that of other human organs, is completed only postnatally when, in response to ovarian hormones (estrogen and progesterone), extensive terminal ductal lobulo-alveolar unit (TDLU) proliferation occurs, resulting in branch extension into the surrounding stroma and lobule differentiation
During normal postnatal mammary gland development and adult remodeling related to the menstrual cycle, pregnancy, and lactation, ovarian hormones and peptide growth factors contribute to the delineation of a definite epithelial cell identity
Accumulating evidence indicates that committed mammary progenitor cells are the bona fide site of breast cancer initiation[2,3], compelling experimental studies have suggested that terminally differentiated cells could acquire malignant features via epithelial-tomesenchymal transition (EMT)[4,5]
Summary
The development of the mammary gland, unlike that of other human organs, is completed only postnatally when, in response to ovarian hormones (estrogen and progesterone), extensive TDLU proliferation occurs, resulting in branch extension into the surrounding stroma and lobule differentiation. The complete functional development of the lobules occurs only with full-term pregnancy and subsequent lactation, at the end of which the lobules involute but retain a larger number of individual alveoli per lobule than were present before pregnancy[9,10]
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