Aromatase Expression in Leptin-Pretreated Human Breast Pre-adipocytes is Enhanced by Zeranol and Suppressed by (-)-Gossypol

作者：Zhong Saiyi; Ye Wei Ping; Xu Ping Ping; Feng Eric; Li Hong; Lin Shu Hong; Liu Jie Yu; Ma Changwei^*; Lin Young C

来源：Anticancer Research, 2010, 30(12): 5077-5084.

• Zeranol
• leptin
• aromatase
• CYP19A1
• estrogen
• human breast pre-adipocytes
• (-)-gossypol

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 (R) 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.

• 出版日期2010-12
• 单位中国农业大学