HER2/Leptin Crosstalk in Breast Cancer

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 leptin/ObR system might contribute to enhanced HER2 activity and reduced sensitivity to anti-HER2 treatments.

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Document Details

Document Type
Technical Report
Publication Date
Sep 01, 2009
Accession Number
ADA516501

Entities

People

  • Eva Surmacz

Organizations

  • Temple University

Tags

DTIC Thesaurus Topics

  • Antibodies
  • Biotechnology
  • Breast Cancer
  • Cell Line
  • Cells
  • Co-Channel Interference
  • Fat Cells
  • Growth Factors
  • Health Services
  • Materials
  • Neoplasms
  • Phosphorylation
  • Proteins
  • Resistance
  • Statistical Analysis
  • Therapy
  • Tumor Cell Line

Fields of Study

  • Biology
  • Medicine

Readers

  • Oncology (Cancer Research).
  • Virology (or Medical Virology).
  • Women's Health and Cancer Risk Research: African American Women and Pregnancy Outcomes.