雷帕霉素对人良性、癌前和恶性乳腺上皮细胞中mTOR信号传导的影响。
Rapamycin effects on mTOR signaling in benign, premalignant and malignant human breast epithelial cells.
作者信息
Kim So Hee, Zukowski Kim, Novak Raymond F
机构信息
Wayne State University, Detroit, MI 48201, USA.
出版信息
Anticancer Res. 2009 Apr;29(4):1143-50.
Rapamycin, an inhibitor of mTOR, is in clinical trials for treatment of cancer. Rapamycin resistance has been reported in human breast epithelial tumor cells. Rapamycin effects on mTOR signaling and resistance were examined using benign, premalignant and tumor human breast epithelial cells. Rapamycin inhibition of cell proliferation, the cell cycle and mTOR signaling, including p70S6 and S6RP phosphorylation, was most effective in benign (MCF10A) and premalignant (MCF10AT; MCF10ATG3B) human breast epithelial cells, relative to MCF10CA1a tumor cells. Rapamycin resistance was reflected by reduced inhibition of p70S6K and S6RP phosphorylation in MCF10CA1a tumor cells, with RS6P showing the least response to rapamycin in the tumor cells. Rapamycin differentially inhibited STAT3 phosphorylation in this cell lineage. These data suggest that inhibition of mTOR signaling and STAT3 phosphorylation in benign and premalignant cells may be effective in the treatment of proliferative breast disease (PBD) and in the prevention of tumorigenesis and tumor recurrence.
雷帕霉素是一种mTOR抑制剂，目前正处于治疗癌症的临床试验阶段。在人乳腺上皮肿瘤细胞中已报道存在雷帕霉素耐药性。使用良性、癌前和肿瘤性人乳腺上皮细胞研究了雷帕霉素对mTOR信号传导和耐药性的影响。相对于MCF10CA1a肿瘤细胞，雷帕霉素对细胞增殖、细胞周期和mTOR信号传导（包括p70S6和S6RP磷酸化）的抑制作用在良性（MCF10A）和癌前（MCF10AT；MCF10ATG3B）人乳腺上皮细胞中最为有效。雷帕霉素耐药性表现为MCF10CA1a肿瘤细胞中p70S6K和S6RP磷酸化的抑制作用减弱，其中RS6P在肿瘤细胞中对雷帕霉素的反应最小。雷帕霉素在该细胞系中对STAT3磷酸化有不同程度的抑制作用。这些数据表明，抑制良性和癌前细胞中的mTOR信号传导和STAT3磷酸化可能对增殖性乳腺疾病（PBD）的治疗以及肿瘤发生和肿瘤复发的预防有效。
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