Leptin as a Potential Target for Estrogen Receptor-Positive Breast Cancer.
10.4048/jbc.2013.16.2.138
- Author:
Cha Kyong YOM
1
;
Kyung Min LEE
;
Wonshik HAN
;
Sung Won KIM
;
Hee Sung KIM
;
Byung In MOON
;
Ku Young JEONG
;
Seock Ah IM
;
Dong Young NOH
Author Information
1. Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.
- Publication Type:Original Article
- Keywords:
Breast neoplasms;
Hormone resistance;
Leptin
- MeSH:
Adipokines;
Blotting, Western;
Breast;
Breast Neoplasms;
Estrogen Receptor Modulators;
Estrogens;
Leptin;
MCF-7 Cells;
Receptors, Leptin;
Signal Transduction;
Tamoxifen
- From:Journal of Breast Cancer
2013;16(2):138-145
- CountryRepublic of Korea
- Language:English
-
Abstract:
PURPOSE: Leptin is a potent adipokine that plays a significant role in tumor development and the progression of breast cancer. The aim of this study was to evaluate whether leptin affects the response to tamoxifen treatment in estrogen receptor (ER)-positive breast cancer cells. METHODS: Leptin, leptin receptor (Ob-R), and activation of signaling pathways were studied by Western immunoblotting. The effects of leptin on tamoxifen-dependent growth inhibition were studied in MCF-7 and T-47D cells. RESULTS: Leptin was expressed in MCF-7 and T-47D and had a proliferative effect on MCF-7 cells. Leptin significantly inhibited the antiestrogenic effect of tamoxifen in both cells only under beta-estradiol (E2) (20 nM) conditions. In MCF-7, the inhibitory effect against tamoxifen was a result from the activation of the ERK1/2 and STAT3 signal transduction pathway. CONCLUSION: Leptin interferes with the effects of tamoxifen under E2 stimulated conditions in ER-positive breast cancer cells. These results imply that inhibition of leptin is expected to enhance the response to tamoxifen in ER-positive breast cancer cells, and, therefore, could be a promising way to overcome endocrine resistance.
