Chronic Leptin Treatment Sensitizes MCF-7 Breast Cancer Cells to Estrogen

被引:14
作者
Valle, Adamo [1 ]
Sastre-Serra, Jorge [1 ]
Oliver, Jordi [1 ]
Roca, Pilar [1 ]
机构
[1] Univ Illes Balears, Dept Biol Fonamental Ciencies Salut 1, Grp Multidisciplinar Oncol Traslac, Inst Univ Invest Ciencies Salut,Inst Salud Carlos, E-07122 Palma De Mallorca, Spain
关键词
Leptin; Estrogen; Breast cancer; Obesity; MCF-7; Estrogen receptor; RECEPTOR-BETA; POSTMENOPAUSAL WOMEN; GENE-EXPRESSION; MAMMARY-TUMORS; GROWTH-FACTOR; FEMALE MICE; CYCLIN D1; OBESITY; ALPHA; IDENTIFICATION;
D O I
10.1159/000335796
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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 (ER alpha and ER beta) 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 ER alpha to ER beta 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 ER alpha to ER beta ratio. Copyright (C) 2011 S. Karger AG, Basel
引用
收藏
页码:823 / 832
页数:10
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