| Author |
Liu, Xihui Shen, Chengyong Bates, Ryan Xiong, Wen-cheng Zhao, Kai Shi, Chao Luo, Shiwen Mei, Jinghong Tao, Yanmei Santoni, Marie-josée Wu, Biao Traoré, Wilfried Mei, Lin Marchetto, Sylvie Xu, Linlin Borg, Jean-paul |
| Description |
Author Affiliation: Tao Y ( Department of Neuroscience and Regenerative Medicine and Department of Neurology, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912); Shen C ( Department of Neuroscience and Regenerative Medicine and Department of Neurology, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912); Luo S ( Center for Experimental Medicine, First Affiliated Hospital of Nanchang University, Nanchang 330006, China); Traoré W ( Cancer Research Center of Marseille, Cell Polarity, Cell Signalling and Cancer 'Equipe labellisée Ligue Contre le Cancer,' INSERM U1068, F-13009 Marseille, France); Marchetto S ( Cancer Research Center of Marseille, Cell Polarity, Cell Signalling and Cancer 'Equipe labellisée Ligue Contre le Cancer,' INSERM U1068, F-13009 Marseille, France); Santoni MJ ( Cancer Research Center of Marseille, Cell Polarity, Cell Signalling and Cancer 'Equipe labellisée Ligue Contre le Cancer,' INSERM U1068, F-13009 Marseille, France); Xu L ( Center for Experimental Medicine, First Affiliated Hospital of Nanchang University, Nanchang 330006, China); Wu B ( Center for Experimental Medicine, First Affiliated Hospital of Nanchang University, Nanchang 330006, China); Shi C ( Center for Experimental Medicine, First Affiliated Hospital of Nanchang University, Nanchang 330006, China); Mei J ( Center for Experimental Medicine, First Affiliated Hospital of Nanchang University, Nanchang 330006, China); Bates R ( Department of Neuroscience and Regenerative Medicine and Department of Neurology, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912); Liu X ( Department of Neuroscience and Regenerative Medicine and Department of Neurology, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912); Zhao K ( Department of Neuroscience and Regenerative Medicine and Department of Neurology, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912); Xiong WC ( Department of Neuroscience and Regenerative Medicine and Department of Neurology, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912); Borg JP ( Cancer Research Center of Marseille, Cell Polarity, Cell Signalling and Cancer 'Equipe labellisée Ligue Contre le Cancer,' INSERM U1068, F-13009 Marseille, France); Mei L ( Department of Neuroscience and Regenerative Medicine and Department of Neurology, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912); |
| Abstract |
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. |
| Subject Keyword |
Adaptor Proteins, Signal Transducing Metabolism Carrier Proteins Receptor, ErbB-2 Animals Antineoplastic Agents Pharmacology Breast Neoplasms Cell Line, Tumor Cell Proliferation Cell Transformation, Neoplastic Disease Progression Gene Deletion Gene Knockdown Techniques HEK293 Cells HSP90 Heat-Shock Proteins Mammary Neoplasms, Experimental Mice Mice, Transgenic Mutation Protein Binding Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
