Aromatase expression in leptin-pretreated human breast pre-adipocytes is enhanced by zeranol and suppressed by (-)-gossypol.
Aromatase expression in leptin-pretreated human breast pre-adipocytes is enhanced by zeranol and suppressed by (-)-gossypol.
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发表时间：
2010-12
影响因子：
2
通讯作者：
Saiyi Zhong;W. Ye;Pingping Xu;Eric Feng;Hong Li;Shu-Hong Lin;Jie-Yu Liu;Changwei Ma;Young C. Lin
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文献类型：
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作者：
Saiyi Zhong;W. Ye;Pingping Xu;Eric Feng;Hong Li;Shu-Hong Lin;Jie-Yu Liu;Changwei Ma;Young C. Lin
背景：肥胖与雌激素依赖性乳腺癌的风险增加有关。最近，zeranol (Z)的作用引起了人们的关注，zeranol是一种非甾体合成代谢生长促进剂，具有强雌激素活性，广泛应用于美国牛肉工业，可能导致人类乳腺癌发病率增加。这项研究假设肥胖个体可能有更大的风险发展zeranol诱导的乳腺癌。材料与方法采用RT-PCR检测三种脂肪组织分离细胞的芳香化酶mRNA表达水平，采用CellTiter96®非放射性方法检测原代培养的人正常乳腺前脂肪细胞（hnbpad）的细胞增殖情况。采用RT-PCR检测Z和棉酚对瘦素预处理hnbpad芳香化酶表达的影响。结果HNBPADs表达的芳香酶高于原代培养的人乳腺上皮细胞和基质细胞。Z增强了瘦素的有丝分裂活性，增加了hnbpad中芳香酶的表达。此外，(-)-棉酚可以抵消Z-和瘦素诱导的细胞增殖和芳香酶表达。结论植入Z型肉牛肉中含有的活性Z代谢物可能通过增加芳香化酶的表达和雌激素的产生，促进肥胖个体雌激素的生物合成，从而促进细胞敏感性，促进乳腺癌细胞生长。
BACKGROUND Obesity is associated with an increased risk of estrogen-dependent breast cancer. Recently, concerns have been raised regarding the role of zeranol (Z), a non-steroidal anabolic growth promoter with potent estrogenic activity widely used in the U.S.A. beef industry, as a possible contributor to an increased incidence of human breast cancer. This study hypothesized that obese individuals may be at greater risk of developing zeranol-induced breast cancer. MATERIALS AND METHODS The aromatase mRNA expression level of three cell types isolated from adipose tissues were assayed by RT-PCR, and the cell proliferation of primary cultured human normal breast pre-adipocytes (HNBPADs) was investigated using the CellTiter96® non-radioactive method. The effects of Z and gossypol on aromatase expression of leptin-pretreated HNBPADs were evaluated by RT-PCR. RESULTS HNBPADs expressed higher aromatase than primary cultured human breast epithelial cells and stromal cells. Z enhanced the mitogenic activity of leptin and increased aromatase expression in HNBPADs. Moreover, (-)-gossypol counteracted Z- and leptin-induced cell proliferation and aromatase expression. CONCLUSION These results suggested that bioactive Z metabolites contained in meat produced from Z-implanted beef cattle may increase estrogen biosynthesis in obese individuals by increasing aromatase expression and estrogen production, which will promote cell sensitivity and increase breast cancer cell growth.