Accession Number:

ADA505199

Title:

Crosstalk Between Leptin Receptor and IGF-IR in Breast Cancer: A Potential Mediator of Chemoresistance

Descriptive Note:

Annual rept. 20 Mar 2008-19 Mar 2009

Corporate Author:

EMORY UNIV ATLANTA GA

Personal Author(s):

• Nahta, Rita

Report Date:

2009-04-01

Pagination or Media Count:

22.0

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.

Descriptors:

• *BREAST CANCER
• *STIMULATION(PHYSIOLOGY)
• *CHEMOTHERAPY
• *RECEPTOR SITES(PHYSIOLOGY)
• INHIBITION
• CELLS(BIOLOGY)
• CROSSTALK
• GROWTH(PHYSIOLOGY)
• OBESITY
• RESPONSE(BIOLOGY)
• MOLECULES
• HUMANS
• RISK
• SURVIVAL(PERSONNEL)

Subject Categories:

• Biochemistry
• Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE