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Publication : Role of Erbin in ErbB2-dependent breast tumor growth.

First Author  Tao Y Year  2014
Journal  Proc Natl Acad Sci U S A Volume  111
Issue  42 Pages  E4429-38
PubMed ID  25288731 Mgi Jnum  J:216431
Mgi Id  MGI:5608807 Doi  10.1073/pnas.1407139111
Citation  Tao Y, et al. (2014) Role of Erbin in ErbB2-dependent breast tumor growth. Proc Natl Acad Sci U S A 111(42):E4429-38
abstractText  ErbB2 (v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2), a receptor tyrosine kinase of the ErbB family, is overexpressed in around 25% of breast cancers. In addition to forming a heterodimer with other ErbB receptors in response to ligand stimulation, ErbB2 can be activated in a ligand-independent manner. We report here that Erbin, an ErbB2-interacting protein that was thought to act as an antitumor factor, is specifically expressed in mammary luminal epithelial cells and facilitates ErbB2-dependent proliferation of breast cancer cells and tumorigenesis in MMTV-neu transgenic mice. Disruption of their interaction decreases ErbB2-dependent proliferation, and deletion of the PDZ domain in Erbin hinders ErbB2-dependent tumor development in MMTV-neu mice. Mechanistically, Erbin forms a complex with ErbB2, promotes its interaction with the chaperon protein HSP90, and thus prevents its degradation. Finally, ErbB2 and Erbin expression correlates in human breast tumor tissues. Together, these observations establish Erbin as an ErbB2 regulator for breast tumor formation and progression.
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