Obesity and Postmenopausal Breast Cancer: Leptin-Estrogen Cross-Talk
Abstract
Obesity is a risk factor for breast cancer development in postmenopausal women and correlates with shorter disease-free and overall survival in breast cancer patients, regardless of menopausal status. Adipose tissue is a major source of leptin, a pluripotent cytokine regulating energy balance and controlling different processes in peripheral tissues, including breast cancer cell growth. In this work, we asked whether leptin can stimulate breast cancer cell growth and counteract anti-tumorigenic activities of the antiestrogen ICI 182,780 (ICI). MCF-7 estrogen receptor alpha (ERalpha)-positive breast cancer cells were used as a model. MCF-7 cells were found to express the signaling form of the leptin receptor and respond to leptin with cell growth and activation the STAT3, ERK1/2, and Akt/GSK3/pRb pathways. As expected, the exposure of cells to 10 nM ICI blocked cell proliferation, induced rapid ERalpha degradation, inhibited nuclear expression of ERalpha, and reduced ERalpha-dependent transcription from estrogen response element-containing promoters. All these effects of ICI were significantly attenuated by simultaneous treatment of cells with l00 ng/ml leptin. We concluded that leptin interferes with the effects of ICI on ERalpha in breast cancer cells. Thus, high leptin levels in obese breast cancer patients might contribute to the development of antiestrogen- resistance.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2004
- Accession Number
- ADA429997
Entities
People
- Eva Surmacz
Organizations
- Thomas Jefferson University