Obesity and the Associated Mediators Leptin, Estrogen and IGF-I Enhance the Cell Proliferation and Early Tumorigenesis of Breast Cancer Cells
Obesity and the Associated Mediators Leptin, Estrogen and IGF-I Enhance the Cell Proliferation and Early Tumorigenesis of Breast Cancer Cells
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DOI：
10.1080/01635580802610115
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发表时间：
2009-06
期刊：
影响因子：
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通讯作者：
A. Lautenbach;A. Budde;C. Wrann;B. Teichmann;G. Vieten;T. Karl;H. Nave
中科院分区：
文献类型：
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作者：
A. Lautenbach;A. Budde;C. Wrann;B. Teichmann;G. Vieten;T. Karl;H. Nave
乳腺癌仍然是妇女癌症死亡的主要原因。雌激素也是由脂肪组织产生的，它是肥胖妇女患乳腺癌风险升高的原因。然而，脂肪组织分泌激素和脂肪因子，如瘦素和IGF-I，这些物质也可能导致肥胖妇女患乳腺癌的风险增加。在这项研究中，研究了肥胖对细胞增殖的影响。向正常体重和饮食诱导的肥胖雌性Sprague-Dawley大鼠给予致癌物7，12-二甲基苯并[a]蒽（DMBA）。通过BrdU掺入的免疫组织化学染色评价细胞增殖。在肥胖大鼠的乳腺和腹股沟淋巴结中，细胞增殖显著增加，表明肥胖对乳腺癌有显著影响。采用MTT法检测瘦素、雌激素和IGF-I对MCF-7细胞增殖的影响。细胞培养实验证明了这三种介质对细胞增殖的促有丝分裂作用。我们的数据证明了脂肪组织产生的物质对乳腺癌的刺激作用。体重特异性细胞增殖表明，肥胖相关的脂肪因子和介质增强细胞增殖，增加乳腺癌的风险。
Breast cancer continues to be a major cause of cancer deaths in women. Estrogen, which is also produced by the adipose tissue, is held responsible for the elevated risk of breast cancer in obese women. However, the adipose tissue secrets hormones and adipokines such as leptin and IGF-I and these substances could also contribute to an increased breast cancer risk for obese women. In this study, the impact of obesity on cell proliferation was investigated. The carcinogen 7, 12, dimethylbenz[a]anthracene (DMBA) was administered to normal weight and diet-induced obese female Sprague-Dawley rats. Cell proliferation was evaluated by immunohistological staining of BrdU-incorporation. In the mammary glands and inguinal lymphatic nodes of the obese rats, cell proliferation was significantly increased, indicating a significant influence of obesity on breast cancer. Effects of leptin, estrogen, and IGF-I on the proliferation of MCF-7 cells in vitro were assessed using an MTT assay. Cell culture experiments demonstrated a mitogenic role of these three mediators on cell proliferation. Our data demonstrate a stimulative effect of substances produced by the adipose tissue on breast cancer. Body weight specific cell proliferation suggests that obesity-related adipokines and mediators enhance cell proliferation and increase the risk for breast cancer.