Crosstalk Between Leptin Receptor and IGF-IR in Breast Cancer: A Potential Mediator of Chemoresistance
Abstract
Obesity is a major risk factor for breast cancer, and is associated with reduced treatment response and reduced overall survival. The obesity-associated hormones IGF-I and leptin and their receptors, IGF-IR and leptin receptor (Ob-R), are elevated in breast cancer. Previously we showed through co-immunoprecipitation and immunoblotting that IGF-IR and Ob-R interact in the breast cancer cell lines MDA-MB-231, MCF7, BT474, and SKBR3. Stimulation of cells with IGF-I promoted Ob-R phosphorylation, which was blocked by IGF-IR kinase inhibition. In addition, IGF-I activated downstream signaling molecules in the leptin receptor and IGF-IR pathways. In contrast to IGF-I, leptin did not induce phosphorylation of IGF-IR, indicating that receptor cross signaling is unidirectional, occurring from IGF-IR to Ob-R. Our results demonstrate for the first time a novel interaction and cross talk between the IGF-I and leptin receptors in human breast cancer cells. Our ongoing studies will examine this cross talk in more detail by determining the biological and molecular effects of inhibition of these growth factor receptors. We will then examine the influence of this cross talk on response to taxane-based chemotherapy.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2009
- Accession Number
- ADA505199
Entities
People
- Rita Nahta
Organizations
- Emory University