Xu Pingping, Ye Weiping, Zhong Saiyi, Jen Robert, Li Hong, Feng Eric, Lin Shu-Hong, Liu Jie-Yu, Lin Young C
Laboratory of Reproductive and Molecular Endocrinology, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA.
Oncol Lett. 2011 Jan;2(1):101-108. doi: 10.3892/ol.2010.214. Epub 2010 Nov 23.
Breast cancer and obesity are serious health problems and their relationship has been studied for many years. Leptin is mainly secreted by adipocytes and plays a key role in breast cancer development. Leptin expression is up-regulated in obese individuals and promotes breast cancer cell growth. On the other hand, exposure to environmental estrogens has been found to be directly related to breast cancer. Zeranol (Z) is a non-steroidal anabolic growth promoter used in the beef industry in the US. This study focused on the evaluation of Z and Z-containing sera (ZS) and its adverse health risk to human consumption of Z-containing meat produced from Z-implanted beef cattle. We hypothesized that Z increases the risk of breast neoplasia in women, particularly in obese women. A cell proliferation assay, ELISA analysis, RT-PCR and Western blot analysis were conducted. Our study demonstrated that Z and ZS collected from Z-implanted heifers stimulated the proliferation of primary cultured human normal breast epithelial cells (HNBECs) by up-regulating cyclin D1 expression. Leptin increased the sensitivity of HNBECs to Z, and Z increased the ability of HNBECs to secrete leptin. These results suggest an interaction between leptin and Z in HNBECs. Furthermore, Z may play a role in leptin-induced breast neoplasia.
乳腺癌和肥胖是严重的健康问题，它们之间的关系已被研究多年。瘦素主要由脂肪细胞分泌，在乳腺癌发展中起关键作用。肥胖个体中瘦素表达上调，并促进乳腺癌细胞生长。另一方面，已发现接触环境雌激素与乳腺癌直接相关。玉米赤霉醇（Z）是美国牛肉行业中使用的一种非甾体类合成代谢生长促进剂。本研究着重评估Z及含Z血清（ZS），以及其对人类食用植入Z的肉牛所产含Z肉类的健康风险。我们假设Z会增加女性尤其是肥胖女性患乳腺肿瘤的风险。进行了细胞增殖测定、酶联免疫吸附测定分析、逆转录-聚合酶链反应及蛋白质免疫印迹分析。我们的研究表明，从植入Z的小母牛收集的Z和ZS通过上调细胞周期蛋白D1表达刺激原代培养的人正常乳腺上皮细胞（HNBECs）增殖。瘦素增加了HNBECs对Z的敏感性，而Z增加了HNBECs分泌瘦素的能力。这些结果表明HNBECs中瘦素与Z之间存在相互作用。此外，Z可能在瘦素诱导的乳腺肿瘤形成中起作用。
