The AMPK-family kinase, Hunk, is required for murine tumorigenesis and metastasis
Breast cancer is the most commonly diagnosed malignancy among women and is the leading cause of cancer-related mortality among women worldwide. Through better understanding of the processes that contribute to cancer incidence and mortality we may be able to develop better therapeutics and therapeutic strategies. Protein kinases regulate a wide range of biological processes, including tumorigenesis, and therapeutics targeting the activity of kinases have been found to be effective in the treatment of human cancers. This dissertation addresses the role of the serine/threonine kinase Hunk ( Hormonally Upregulated, Neu-tumor associated Kinase) in the processes of breast cancer progression and metastasis. ^ We recently identified Hunk, an AMPK-family kinase, expressed in the mammary gland during pregnancy. To address the role of Hunk in mammary tumorigenesis and metastasis we assessed the role of Hunk in c-Myc and HER2/neu-induced mammary tumorigenesis in genetically engineered mice. Hunk-deficient animals demonstrate a decreased incidence of c-Myc-induced mammary tumor metastasis with no observed defects in primary mammary tumorigenesis. Hunk-deficient tumor cells display a defect in cellular migration and invasion, and exogenous expression of Hunk in these cells can restore their metastatic potential. In contrast to c-Myc-induced mammary tumorigenesis, Hunk is required for neu-induced primary tumorigenesis as Hunk-deficient animals display increased tumor latency and decreased tumor multiplicity. In the absence of Hunk, expression of Er81---a member of the Pea3 family of transcription factors whose activity has been shown to be essential for neu-induced mammary tumor formation---fails to be upregulated by neu. These results identify HUNK as a critical regulator of breast cancer progression and as a potential therapeutic target in the treatment of HER2-amplified and metastatic breast cancers. ^
Biology, Molecular|Biology, Cell|Health Sciences, Oncology
Thomas W Yang,
"The AMPK-family kinase, Hunk, is required for murine tumorigenesis and metastasis"
(January 1, 2005).
Dissertations available from ProQuest.