Activation and function of the epidermal growth factor receptor and erbB-2 during mammary gland morphogenesis

Joseph Sebastian, R. Gregg Richards, Michael P. Walker, Jane Wiesen, Zena Werb, Rik Derynck, Yun K. Hom, Gerald R. Cunha, Richard P. DiAugustine

Research output: Contribution to journalArticle

103 Citations (Scopus)

Abstract

The hormonal stimulation of mammary gland morphogenesis is believed to occur through growth factor receptor signaling pathways. To determine the importance of the epidermal growth factor receptor (EGFR) pathway, we examined extracts of inguinal mammary glands from prepubertal and pubertal mice for tyrosine-phosphorylated EGFR and other erbB receptors. Tyrosine phosphorylation of both EGFR and erbB-2 was detected in normal female BALB/c mice at 5-6 weeks of age, but not during the prepubertal stage, e.g., 24 days of age. Treatment of mice with estradiol or epidermal growth factor also stimulated the formation of mammary EGFR/erbB-2 phosphotyrosine. Waved-2 mice, which have impaired EGFR kinase activity, exhibited less mammary development than did wild-type (wt) mice when both were evaluated at 36 days of age. Because EGFR knockout (KO) mice die shortly after birth, glands from the newborns were implanted under the renal capsules of female nude mice. Under these conditions, extensive ductal growth was observed in mammary glands from wt animals; in contrast, glands from EGFR KO mice failed to grow beyond rudimentary structures. Tissue recombinants revealed that the wt fat pad supported the morphogenesis of EGFR KO epithelium, whereas the EGFR KO fat pad did not. Taken together, these data suggest that EGFR is essential for morphogenesis of the mammary ducts and functions during this period of mammary development as a heterodimer with erbB-2 in the mammary stroma.

Original languageEnglish (US)
Pages (from-to)777-785
Number of pages9
JournalCell Growth and Differentiation
Volume9
Issue number9
StatePublished - Sep 1998
Externally publishedYes

Fingerprint

Human Mammary Glands
Morphogenesis
Epidermal Growth Factor Receptor
Breast
Knockout Mice
Tyrosine
Adipose Tissue
Phosphotyrosine
Wild Animals
Growth Factor Receptors
Groin
Epidermal Growth Factor
Nude Mice
Capsules
Estradiol
Epithelium
Phosphorylation
Parturition
Kidney

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Sebastian, J., Richards, R. G., Walker, M. P., Wiesen, J., Werb, Z., Derynck, R., ... DiAugustine, R. P. (1998). Activation and function of the epidermal growth factor receptor and erbB-2 during mammary gland morphogenesis. Cell Growth and Differentiation, 9(9), 777-785.

Activation and function of the epidermal growth factor receptor and erbB-2 during mammary gland morphogenesis. / Sebastian, Joseph; Richards, R. Gregg; Walker, Michael P.; Wiesen, Jane; Werb, Zena; Derynck, Rik; Hom, Yun K.; Cunha, Gerald R.; DiAugustine, Richard P.

In: Cell Growth and Differentiation, Vol. 9, No. 9, 09.1998, p. 777-785.

Research output: Contribution to journalArticle

Sebastian, J, Richards, RG, Walker, MP, Wiesen, J, Werb, Z, Derynck, R, Hom, YK, Cunha, GR & DiAugustine, RP 1998, 'Activation and function of the epidermal growth factor receptor and erbB-2 during mammary gland morphogenesis', Cell Growth and Differentiation, vol. 9, no. 9, pp. 777-785.
Sebastian J, Richards RG, Walker MP, Wiesen J, Werb Z, Derynck R et al. Activation and function of the epidermal growth factor receptor and erbB-2 during mammary gland morphogenesis. Cell Growth and Differentiation. 1998 Sep;9(9):777-785.
Sebastian, Joseph ; Richards, R. Gregg ; Walker, Michael P. ; Wiesen, Jane ; Werb, Zena ; Derynck, Rik ; Hom, Yun K. ; Cunha, Gerald R. ; DiAugustine, Richard P. / Activation and function of the epidermal growth factor receptor and erbB-2 during mammary gland morphogenesis. In: Cell Growth and Differentiation. 1998 ; Vol. 9, No. 9. pp. 777-785.
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