Leptin receptor expression and cell signaling in breast cancer.
Leptin receptor expression and cell signaling in breast cancer.
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DOI：
10.3892/ijo.28.4.985
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发表时间：
2006-04
影响因子：
5.2
通讯作者：
K. Frankenberry;H. Skinner;P. Somasundar;D. Mcfadden;L. Vona-Davis
中科院分区：
文献类型：
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作者：
K. Frankenberry;H. Skinner;P. Somasundar;D. Mcfadden;L. Vona-Davis
肥胖被认为是许多癌症的危险因素，包括乳腺癌。我们的实验室先前已经表明，瘦素是有丝分裂在许多癌细胞系，包括乳腺癌。缺乏关于高瘦素水平对瘦素受体表达和信号传导的影响的信息。本研究的目的是描述乳腺癌细胞中瘦素受体表达对瘦素的反应。此外，还检测了SOCS-3表达（瘦素诱导的瘦素信号传导抑制剂）以及MAPK和PI 3 K信号传导，以确定它们在瘦素诱导的细胞增殖中的作用。乳腺癌细胞系ZR 75 -1和HTB-26用0、4、40或80 ng/ml的瘦素处理。进行多重RT-PCR以确定人短（huOB-Ra）或长（huOB-Rb）瘦素受体同种型或SOCS-3的相对mRNA表达水平。通过蛋白质印迹法分别通过ERK和Akt的磷酸化来分析MAPK和PI 3 K信号传导。MTT法检测细胞增殖和抑制因子。HTB-26和ZR 75 -1均表达huOB-Ra、huOB-Rb和SOCS-3 mRNA;然而，mRNA表达水平通常在瘦素处理下随时间保持不变。MAPK和PI 3 K通路在瘦素存在下随时间被激活。MAPK和PI 3 K抑制剂显著阻断瘦素诱导的增殖。较高水平的循环瘦素通过激活参与细胞生长和存活的MAPK和PI 3 K信号通路而促进乳腺癌增殖。瘦素的促有丝分裂作用不是改变瘦素受体或SOCS-3 mRNA表达的结果。
Obesity is considered a risk factor for many cancers, including breast cancer. Our laboratory has previously shown that leptin is mitogenic in many cancer cell lines, including breast. Information regarding the effects of high leptin levels on leptin receptor expression and signaling is lacking. The purpose of this study was to characterize leptin receptor expression in response to leptin in breast cancer cells. In addition, SOCS-3 expression (a leptin inducible inhibitor of leptin signaling), plus MAPK and PI3K signaling, were examined to determine their role in leptin-induced cell proliferation. Breast cancer cell lines, ZR75-1 and HTB-26, were treated with 0, 4, 40 or 80 ng/ml of leptin. Multiplex RT-PCR was performed to determine relative mRNA expression levels of the human short (huOB-Ra) or long (huOB-Rb) leptin receptor isoforms, or SOCS-3. MAPK and PI3K signaling was analyzed by phosphorylation of ERK and Akt, respectively, via Western blotting. Cell proliferation and inhibitor studies were analyzed by MTT assay. HTB-26 and ZR75-1 both expressed huOB-Ra, huOB-Rb and SOCS-3 mRNA; however, mRNA expression levels generally remained unchanged over time with leptin treatment. MAPK and PI3K pathways were activated in the presence of leptin over time. MAPK and PI3K inhibitors significantly blocked leptin-induced proliferation. Higher levels of circulating leptin contribute to breast cancer proliferation by activation of the MAPK and PI3K signaling pathways involved in cell growth and survival. The mitogenic effects of leptin are not a consequence of altered leptin receptor or SOCS-3 mRNA expression.