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- Title
Chronic Leptin Treatment Sensitizes MCF-7 Breast Cancer Cells to Estrogen.
- Authors
Valle, Adamo; Sastre-Serra, Jorge; Oliver, Jordi; Roca, Pilar
- Abstract
Background/Aims: Obesity is associated with an increased risk of estrogen-dependent breast cancer. The adipokine leptin, whose levels are chronically increased in obese people, has been shown to stimulate ER positive cancer cell growth. Considering previous evidence of a crosstalk between leptin and estrogen signaling, the objective of this study was to establish the influence of chronic leptin treatment on estrogen-dependent cell growth. Methods: To this aim, we use the estrogen receptor (ER) positive MCF-7 breast cancer cell line treated chronically with leptin and analyzed estrogen-dependent cell growth, ERs (ERα and ERβ) expression, ER-dependent transcriptional activity as well as cell survival to the antiestrogenic agents tamoxifen and ICI 182,780. Results: Leptin signaling pathway kept activated after chronic stimulation (7 days) with leptin showing significant phosphorylation of JAK2 and STAT3 and higher cell proliferation rate. Chronic leptin at 100 ng/mL dose increased ERα to ERβ ratio and consistently enhanced estrogen-dependent transcriptional activity, increasing E2-dependent cell growth and resistance to antiestrogen agents. Conclusion: This study supports the existence of a crosstalk between leptin and estrogen, in which leptin might play an important role potentiating the mitogenic action of estrogen, probably by alteration of ERα to ERβ ratio. Copyright © 2011 S. Karger AG, Basel
- Subjects
OBESITY risk factors; LEPTIN; BREAST cancer; CANCER cells; CELL growth; ESTROGEN; CELLULAR signal transduction
- Publication
Cellular Physiology & Biochemistry (Karger AG), 2011, Vol 28, Issue 5, p823
- ISSN
1015-8987
- Publication type
Article
- DOI
10.1159/000335796