Roles of Fas and Fas ligand during mammary gland remodeling
Joon Song, … , Frederick Naftolin, Gil Mor
Joon Song, … , Frederick Naftolin, Gil Mor
Published November 15, 2000
Citation Information: J Clin Invest. 2000;106(10):1209-1220. https://doi.org/10.1172/JCI10411.
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Article

Roles of Fas and Fas ligand during mammary gland remodeling

Abstract

Mammary involution is associated with degeneration of the alveolar structure and programmed cell death of mammary epithelial cells. In this study, we evaluated the expression of Fas and Fas ligand (FasL) in the mammary gland tissue and their possible role in the induction of apoptosis of mammary cells. FasL-positive cells were observed in normal mammary epithelium from pregnant and lactating mice, but not in nonpregnant/virgin mouse mammary tissue. Fas expression was observed in epithelial and stromal cells in nonpregnant mice but was absent during pregnancy. At day 1 after weaning, high levels of both Fas and FasL proteins and caspase 3 were observed and coincided with the appearance of apoptotic cells in ducts and glands. During the same period, no apoptotic cells were found in the Fas-deficient (MRL/lpr) and FasL-deficient (C3H/gld) mice. Increase in Fas and FasL protein was demonstrated in human (MCF10A) and mouse (HC-11) mammary epithelial cells after incubation in hormone-deprived media, before apoptosis was detected. These results suggest that the Fas-FasL interaction plays an important role in the normal remodeling of mammary tissue. Furthermore, this autocrine induction of apoptosis may prevent accumulation of cells with mutations and subsequent neoplastic development. Failure of the Fas/FasL signal could contribute to tumor development.

Authors

Joon Song, Eva Sapi, Wendi Brown, Jon Nilsen, Karrie Tartaro, Barry M. Kacinski, Joseph Craft, Frederick Naftolin, Gil Mor

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Figure 2

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Expression of Fas/FasL protein in mouse mammary tissue. Western blot ana...
Expression of Fas/FasL protein in mouse mammary tissue. Western blot analysis for Fas and FasL was performed with protein samples obtained from the same samples described in Figure 1. Fas expression is found in breasts from virgin mice but is not expressed during pregnancy and lactation. High levels of Fas protein appear 1 day after weaning. FasL is expressed during pregnancy, lactation, and involution, but not in the virgin mouse. The intensity of the signal was analyzed using a digital imaging analysis system. Bars represent the average ± SD from three independent experiments. The figure of the immunoblot is a representative experiment of the three experiments. Lane 1, virgin; lane 2, day 15 of pregnancy; lane 3, day 19 of pregnancy; lane 4, day 10 of lactation; lane 5, day 1 AW; lane 6, day 2 AW; lane 7, day 4 AW; lane 8, day 12 AW.