Oncogene-Induced Changes in Mammary Cell Fate and EMT in Breast Tumorigenesis
Annual rept. 15 Mar 2014-14 Mar 2015
PITTSBURGH UNIV PA
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Basal-liketriple negative breast cancers TNBCs are characterized by distinctive features most closely resembling basalmyoepithelial cells however, it is still unclear from which mammary lineage these tumors are derived. Insulin-like growth factor receptor I IGF1R is overexpressed and amplified in TNBCs, correlating with poor prognosis, and TNBCs are especially sensitive to IGF1RInsulin receptor inhibition. Our novel mouse model for retroviral introduction of IGF1R into the mammary gland demonstrates that IGF1R induces basal-like mammary tumors with mixed histologies, including a dramatic expansion of a rare population positive for both luminal CK8 and myoepithelial CK14 markers. My preliminary data previously indicated that IGF1R promotes self-renewal and differentiated progeny. The approach proposed in this fellowship is to utilize IGF1R-induced tumor heterogeneity as a model system to help identify how cell of origin and molecular alterations change mammary cell fate to produce heterogeneous mammary tumors. Here, I describe my progress in determining the mechanism of IGF1R-promoted tumor initiation characteristics, whether IGF1R alters self-renewal, and if IGF1R expression in breast tumors correlates with tumor initiation and cell fate markers.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research