Oncogene-Induced Changes in Mammary Cell Fate and EMT in Breast Tumorigenesis
Abstract
Basal-like/triple negative breast cancers (TNBCs) are characterized by distinctive features most closely resembling basal/myoepithelial 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 IGF1R/Insulin 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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2015
- Accession Number
- ADA621438
Entities
People
- Susan M. Farabaugh
Organizations
- University of Pittsburgh