Rebecca Cook
Faculty Member
Last active: 4/15/2019

The receptor tyrosine kinase ErbB3 maintains the balance between luminal and basal breast epithelium.

Balko JM, Miller TW, Morrison MM, Hutchinson K, Young C, Rinehart C, Sánchez V, Jee D, Polyak K, Prat A, Perou CM, Arteaga CL, Cook RS
Proc Natl Acad Sci U S A. 2012 109 (1): 221-6

PMID: 22178756 · PMCID: PMC3252958 · DOI:10.1073/pnas.1115802109

ErbB3 harbors weak kinase activity, but strongly activates downstream phosphatidylinositol 3-kinase/Akt signaling through heterodimerization with and activation by other ErbB receptor tyrosine kinases. We report here that ErbB3 loss in the luminal mammary epithelium of mice impaired Akt and MAPK signaling and reduced luminal cell proliferation and survival. ERBB3 mRNA expression levels were highest in luminal mammary populations and lowest in basal cell/stem cell populations. ErbB3 loss in mammary epithelial cells shifted gene expression patterns toward a mammary basal cell/stem cell signature. ErbB3 depletion-induced gene expression changes were rescued upon activation of Akt and MAPK signaling. Interestingly, proliferation and expansion of the mammary basal epithelium (BE) occurred upon ErbB3 targeting in the luminal epithelium, but not upon its targeting in the BE. Multiple cytokines, including interleukin 6, were induced upon ErbB3 depletion in luminal epithelium cells, which increased growth of BE cells. Taken together, these results suggest that ErbB3 regulates the balance of differentiated breast epithelial cell types by regulating their growth and survival through autocrine- and paracrine-signaling mechanisms.

MeSH Terms (17)

Animals Biomarkers Cell Line, Transformed Cell Proliferation Cell Survival Epithelial Cells Epithelium Female Interleukin-6 Mammary Glands, Animal MAP Kinase Signaling System Mice Mitogen-Activated Protein Kinases Phenotype Phosphatidylinositol 3-Kinases Phosphorylation Receptor, ErbB-3

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