MDM2过表达在乳腺癌阿霉素耐药中的作用
Role of MDM2 overexpression in doxorubicin resistance of breast carcinoma.
作者信息
Suzuki A, Toi M, Yamamoto Y, Saji S, Muta M, Tominaga T
机构信息
Department of Surgery, Tokyo Metropolitan Komagome Hospital.
出版信息
Jpn J Cancer Res. 1998 Feb;89(2):221-7. doi: 10.1111/j.1349-7006.1998.tb00552.x.
Several oncoproteins or tumor suppressor gene products have been indicated to be of value as predictors of the de novo resistance to cytotoxic agents. In this study, we have investigated the role of MDM2 (murine double minutes) overexpression in doxorubicin resistance of breast cancer. Immunocytochemical analysis demonstrated that MDM2-positive tumors, even with p53-negative phenotype, were significantly more resistant to doxorubicin treatment compared to MDM2-negative tumors. An in vitro experimental model using stable mdm2-transfected MCF-7 cells carrying wild-type p53 confirmed that the cells become approximately 3-fold more resistant to doxorubicin as a result of MDM2 overexpression, and the wild-type p53 function, such as the induction of p21Waf1 following DNA damage, was significantly suppressed. MDM2 overexpression is suggested to be a novel marker for predicting lack of response to doxorubicin treatment in breast cancer patients.
几种癌蛋白或肿瘤抑制基因产物已被证明可作为对细胞毒性药物原发性耐药的预测指标。在本研究中，我们调查了MDM2（小鼠双微体）过表达在乳腺癌阿霉素耐药中的作用。免疫细胞化学分析表明，MDM2阳性肿瘤，即使具有p53阴性表型，与MDM2阴性肿瘤相比，对阿霉素治疗的耐药性明显更强。使用稳定转染mdm2且携带野生型p53的MCF-7细胞建立的体外实验模型证实，由于MDM2过表达，细胞对阿霉素的耐药性增加了约3倍，并且野生型p53功能，如DNA损伤后p21Waf1的诱导，受到显著抑制。MDM2过表达被认为是预测乳腺癌患者对阿霉素治疗无反应的一个新标志物。
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