Roles of Fas and Fas ligand during mammary gland remodeling

Mammary involution is associated with degeneration of the alveolar structur e and programmed cell death of mammary epithelial cells. In this study we e valuated the expression of Fas and Fas ligand (FasL) in the mammary gland t issue and their possible role in the induction of apoptosis of mammary cell s. Fast-positive cells were observed in normal mammary epithelium from preg nant and lactating mice, but not in nonpregnant/virgin mouse mammary tissue . Fas expression was observed in epithelial and stromal cells in nonpregnan t mice but was absent during pregnancy. At day 1 after weaning, high levels of both Fas and FasL proteins and caspase 3 mere observed and coincided wi th the appearance of apoptotic cells in ducts and glands. During the same p eriod, no apoptotic cells were found in the Fas-deficient (MRL/lpr) and Fas L-deficient (C3H/gld) mice. Increase in Fas and FasL protein was demonstrat ed in human (MCF10A) and mouse (HC-11) mammary epithelial cells after incub ation in hormone-deprived media, before apoptosis was detected. These resul ts suggest that the Fas-FasL interaction plays an important role in the nor mal remodeling of mammary tissue. Furthermore, this autocrine induction of apoptosis may prevent accumulation of cells with mutations and subsequent n eoplastic development. Failure of the Fas/FasL signal could contribute to t umor development.