Abstract
Background: Obesity is a well-known factor risk for breast cancer in postmenopausal women. Circulating leptin levels are increased in obese and it has been suggested to play an important role in mammary tumor formation and progression. To contribute to the understanding of the molecular mechanisms underlying leptin action in breast cancer, our aim was to identify proteins regulated by leptin in MCF-7 human breast cancer cells.Methods: We used two-dimensional gel electrophoresis (2-DE) and matrix assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) to identify proteins affected by leptin.Results: Thirty proteins were found differentially expressed in MCF-7 cells after 48 h leptin exposure. Proteins regulated by leptin included proteins previously implicated in breast cancer such as catechol-o-methyltransferase, cathepsin D, hsp27, serine/threonine-protein phosphatase and regulatory proteins of the Ras signaling pathway. Proteins involved in other cellular functions such as stress response, cytosqueleton remodeling and proteins belonging to ubiquitin-proteasome system, were also identified. Furthermore, leptin-treated cells showed a substantial uptake of the serum carrier proteins albumin and alpha-2-HS-glycoprotein.Conclusions: This screening reveals that leptin influences the levels of key proteins involved in breast cancer which opens new avenues for the study of the molecular mechanisms linking obesity to breast cancer.
Highlights
Obesity has been associated to increased risk of breast cancer in postmenopausal women [1,2,3]
Concentrations of 50 ng/ml of leptin were chosen to represent levels that would be found in an obese postmenopausal woman [24, 25] and were used for subsequent experiments
Cell cycle state was evaluated by flow cytometry to check that leptin stimulation resulted in cell cycle progression that is characterized by a decrease in cells in G0/G1 and an increase in cells in S and G2/M phases [26]
Summary
Obesity has been associated to increased risk of breast cancer in postmenopausal women [1,2,3]. It has been proposed that increased exposure of mammary epithelial cells to several growth factors and hormones, such as estrogens, insulin-like growth factor-I (IGF-I) and leptin might be potential contributing factors to breast cancer pathogenesis in obese women. The role of estrogen, insulin and IGF-1 in breast cancer has been extensively studied, the potential role of leptin is just beginning to be characterized [5]. To contribute to the understanding of the molecular mechanisms underlying leptin action in breast cancer, our aim was to identify proteins regulated by leptin in MCF-7 human breast cancer cells
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