Roles of Fas and Fas ligand during mammary gland remodeling.
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.
Song
J
J
Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Sapi
E
E
Brown
W
W
Nilsen
J
J
Tartaro
K
K
Kacinski
B M
BM
Craft
J
J
Naftolin
F
F
Mor
G
G
D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western / Q000379:methods; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D003470:Culture Media; D016895:Culture Media, Serum-Free; D003907:Dexamethasone / Q000378:metabolism / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D053222:Fas Ligand Protein; D005260:Female; D015870:Gene Expression; D006801:Humans; D008321:Mammary Glands, Animal / Q000378:metabolism / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D019463:Mice, Inbred MRL lpr; D018345:Mice, Knockout; D011247:Pregnancy; D011270:Pregnancy, Animal; D012333:RNA, Messenger; D019014:fas Receptor / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*
D003470:Culture Media; D016895:Culture Media, Serum-Free; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D019014:fas Receptor; D003907:Dexamethasone; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases