Hormonal induction and roles of disabled-2 in lactation and involution

Wensi Tao, Robert Moore, Elizabeth R. Smith, Xiangxi Xu

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Disabled-2 (Dab2) is a widely expressed endocytic adaptor that was first isolated as a 96 KDa phospho-protein, p96, involved in MAPK signal transduction. Dab2 expression is lost in several cancer types including breast cancer, and Dab2 is thought to have a tumor suppressor function. In mammary epithelia, Dab2 was induced upon pregnancy and further elevated during lactation. We constructed mutant mice with a mosaic Dab2 gene deletion to bypass early embryonic lethality and to investigate the roles of Dab2 in mammary physiology. Loss of Dab2 had subtle effects on lactation, but Dab2-deficient mammary glands showed a strikingly delayed cell clearance during involution. In primary cultures of mouse mammary epithelial cells, Dab2 proteins were also induced by estrogen, progesterone, and/or prolactin. Dab2 null mammary epithelial cells were refractory to growth suppression induced by TGF-beta. However, Dab2 deletion did not affect Smad2 phosphorylation; rather TGF-beta-stimulated MAPK activation was enhanced in Dab2-deficient cells. We conclude that Dab2 expression is induced by hormones and Dab2 plays a role in modulating TGF-beta signaling to enhance apoptotic clearance of mammary epithelial cells during involution.

Original languageEnglish
Article numbere110737
JournalPLoS One
Volume9
Issue number10
DOIs
StatePublished - Oct 31 2014

Fingerprint

Lactation
Transforming Growth Factor beta
breasts
Breast
lactation
transforming growth factor beta
epithelial cells
Epithelial Cells
Signal transduction
Phosphorylation
Physiology
Prolactin
Refractory materials
Progesterone
Tumors
Breast Neoplasms
Estrogens
Proteins
Genes
Chemical activation

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Hormonal induction and roles of disabled-2 in lactation and involution. / Tao, Wensi; Moore, Robert; Smith, Elizabeth R.; Xu, Xiangxi.

In: PLoS One, Vol. 9, No. 10, e110737, 31.10.2014.

Research output: Contribution to journalArticle

Tao, Wensi ; Moore, Robert ; Smith, Elizabeth R. ; Xu, Xiangxi. / Hormonal induction and roles of disabled-2 in lactation and involution. In: PLoS One. 2014 ; Vol. 9, No. 10.
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