Maintenance of Epithelial Stem Cells by Cbl Proteins
Annual rept. 1 Sep 2011-31 Aug 2011
NEBRASKA UNIV MEDICAL CENTER OMAHA
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The Cbl family E3 ubiquitin ligases are critical regulators of tyrosine kinase-mediated signal transduction, and we and others demonstrated that the Cbl family proteins were required to maintain the homeostasis of the hematopoietic stem cell compartment and disturbance of this critical regulatory pathway led to cancer in human and mice. However, their roles in the epithelial stemprogenitor cells has never been examined. Using the newly-established hTERT-immortalized human mammary epithelial cell hMEC line hereafter called TERT-hMEC, we demonstrated that loss of Cbl inhibited differentiation of epithelial cells. Our preliminary studies indicate that Cbl functions in multiple signaling pathways beyond the traditional EGFR pathway, which appears to be responsible for the complex phenotypes of Cbl deficiency in the epithelial compartment.
- Medicine and Medical Research