Hunk is required for HER2/neu-induced mammary tumorigenesis

摘要: Understanding the molecular pathways that contribute to aggressive behavior of human cancers is a critical research priority. The SNF1/AMPK-related protein kinase Hunk overexpressed in subsets breast, ovarian, and colon cancers. Analysis Hunk(–/–) mice revealed this required for metastasis c-myc–induced mammary tumors but not primary tumor formation. Similar c-myc, amplification proto-oncogene HER2/neu occurs 10%–30% breast associated with behavior. By crossing transgenic mouse models HER2/neu-induced tumorigenesis, we report formation induced by HER2/neu. Knockdown reconstitution experiments cancer cell lines demonstrated maintenance tumorigenic phenotype HER2/neu-transformed cells. This requirement dependent resulted from ability suppress apoptosis association downregulation suppressor p27(kip1). Additionally, find rapidly upregulated following activation vivo vitro. These findings provide what believe first evidence role tumorigenesis survival identify as an essential effector oncogenic pathway.