Expression and functional properties of transforming growth factor alpha and epidermal growth factor during mouse mammary gland ductal morphogenesis.
Primer-directed enzyme amplification was used to examine epidermal growth factor (EGF) and transforming growth factor alpha (TGF-alpha) mRNA transcripts in mammary glands of young virgin, mature virgin, midpregnant, and midlactating mice. Transcripts for both EGF and TGF-alpha mRNA were detected in virgin and pregnant mice, whereas transcripts for EGF mRNA but not TGF-alpha mRNA were expressed in 10-day lactating mice. TGF-alpha was localized in the epithelial cap-cell layer of the advancing terminal end bud and in the stromal fibroblasts at the base of the terminal end bud; EGF was localized in the inner layers of the terminal end bud and in ductal cells of mammary epithelium. Implantation of pellets containing EGF or TGF-alpha into the regressed mammary gland of ovariectomized mice stimulated the reappearance of end buds; contralateral glands implanted with pellets containing albumin or insulin were not affected. These results indicate that an EGF-receptor-mediated pathway remained intact in the mammary gland epithelium in the absence of ovarian steroids and that local availability of either EGF or TGF-alpha is sufficient to stimulate the pattern of normal ductal growth. The detection of EGF and TFF-alpha transcripts at different stages of mammary gland development and the different patterns of immunolocalization suggest that each polypeptide plays a different role in normal mammary gland morphogenesis.
Snedeker
S M
SM
Laboratory of Biochemical Risk Analysis, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709.
Brown
C F
CF
DiAugustine
R P
RP
D000818:Animals; D001483:Base Sequence; D004815:Epidermal Growth Factor / Q000235:genetics* / Q000494:pharmacology / Q000502:physiology; D005260:Female; D007774:Lactation / Q000502:physiology*; D008321:Mammary Glands, Animal / Q000166:cytology / Q000187:drug effects / Q000254:growth & development*; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D009024:Morphogenesis; D015345:Oligonucleotide Probes; D010052:Ovariectomy; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D012741:Sexual Maturation; D014158:Transcription, Genetic; D016211:Transforming Growth Factor alpha / Q000235:genetics* / Q000494:pharmacology / Q000502:physiology
D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D016211:Transforming Growth Factor alpha; D004815:Epidermal Growth Factor