Accession Number:

ADA516501

Title:

HER2/Leptin Crosstalk in Breast Cancer

Descriptive Note:

Final rept. 1 Sep 2007-30 Aug 2009

Corporate Author:

TEMPLE UNIV PHILADELPHIA PA

Personal Author(s):

• Surmacz, Eva

Report Date:

2009-09-01

Pagination or Media Count:

20.0

Abstract:

Obesity in postmenopausal women is associated with increased breast cancer risk, development of more aggressive tumors and resistance to certain anti-breast cancer treatments. These effects might be mediated by obesity hormone leptin. Here we investigated if leptin can transactivate the oncogenic receptor HER2 and interfere with the activity of anti-HER2 antibody. We found that HER2 and the leptin receptor ObR are coexpressed in several studied breast cancer cell lines. In MCF-7 cells, HER2 physically interacted with ObR and leptin treatment increased HER2 phosphorylation on Tyr 1248. Furthermore, leptin reduced the efficacy of anti- HER2 drug Herceptin. Studies of human breast cancers revealed that the presence of leptin correlated with ObR, and the whole leptin system was coexpressed with HER2 in 50 of all tumors. Thus, coexpression of HER2 and the leptinObR system might contribute to enhanced HER2 activity and reduced sensitivity to anti-HER2 treatments.

Descriptors:

• *OBESITY
• *BREAST CANCER
• HUMANS
• NEOPLASMS
• SENSITIVITY
• CELLS(BIOLOGY)
• WOMEN
• CROSSTALK
• RISK
• HORMONES
• REDUCTION

Subject Categories:

• Anatomy and Physiology
• Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE