Dual Roles of the Transcription Factor Grainyhead-like 2 (GRHL2) in Breast Cancer

摘要: Using a retrovirus-mediated cDNA expression cloning approach, we identified the grainyhead-like 2 (GRHL2) transcription factor as novel protooncogene. Overexpression of GRHL2 in NIH3T3 cells induced striking morphological changes, an increase cell proliferation, anchorage-independent growth, and tumor growth vivo. By combining microarray analysis phylogenetic footprinting with various biochemical assays, epidermal receptor family member Erbb3 target gene. In breast cancer lines, shRNA-mediated knockdown or functional inactivation using dominant negative proteins induces down-regulation ERBB3 gene expression, reduction phenotypical alterations characteristic epithelial-to-mesenchymal transition (EMT), thus implying contradictory roles carcinogenesis. Interestingly, could further demonstrate that is directly suppressed by zinc finger enhancer-binding protein 1 (ZEB1), which turn direct for repression GRHL2, suggesting EMT factors ZEB1 form double regulatory feedback loop cells. Finally, comprehensive immunohistochemical primary cancers showed loss at invasive front tumors. A pathophysiological relevance metastasis demonstrated our finding statistically significant association between lymph node metastasis. We crucial role