Radiotherapy modulates expression of EGFR, ERCC1 and p53 in cervical cancer.
Radiotherapy modulates expression of EGFR, ERCC1 and p53 in cervical cancer.
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DOI：
10.1590/1414-431x20176822
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发表时间：
2017-11-13
期刊：
影响因子：
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通讯作者：
Sternberg C
中科院分区：
文献类型：
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作者：
de Almeida VH;de Melo AC;Meira DD;Pires AC;Nogueira-Rodrigues A;Pimenta-Inada HK;Alves FG;Moralez G;Thiago LS;Ferreira CG;Sternberg C
宫颈癌是一个公共卫生问题，其放射抗性的分子机制仍然知之甚少。在这里，我们评估了宫颈癌细胞系（CASKI和C33 A）和10例患者放疗前后活检的恶性组织中参与细胞增殖、细胞周期和DNA修复的关键分子的调节。采用定量PCR和免疫印迹法检测表皮生长因子受体（EGFR）、切除修复交叉互补组1（ERCC 1）和p53在癌细胞系中的表达，采用免疫组化法检测人恶性肿瘤组织中EGFR、ERCC 1和p53的表达。直接测序法检测TP 53基因突变情况。在细胞系中，观察到暴露于1.8戈伊后EGFR、ERCC 1和p53的缺失或弱调节。在相同剂量的放疗后，p53（5/10例患者; P=0.0239）、ERCC 1（5/10例患者; P=0.0294）和EGFR（4/10例患者; P=0.1773）在恶性肿瘤组织中的表达明显增加。TP 53突变仅在1例患者中发现。在这里，我们表明，一个单一剂量的放射治疗诱导EGFR，ERCC 1和p53的表达在宫颈癌患者的恶性组织中，而不是在癌细胞系，突出体外和体内实验模型之间的差距。需要对更大的患者队列进行研究，以解释p53，EGFR和ERCC 1的上调可能是放射抗性机制的一部分。
Cervical cancer is a public health problem and the molecular mechanisms underlying radioresistance are still poorly understood. Here, we evaluated the modulation of key molecules involved in cell proliferation, cell cycle and DNA repair in cervical cancer cell lines (CASKI and C33A) and in malignant tissues biopsied from 10 patients before and after radiotherapy. The expression patterns of epidermal growth factor receptor (EGFR), excision repair cross-complementation group 1 (ERCC1) and p53 were evaluated in cancer cell lines by quantitative PCR and western blotting, and in human malignant tissues by immunohistochemistry. The mutation status of TP53 gene was evaluated by direct sequencing. Among cell lines, absent or weak modulations of EGFR, ERCC1 and p53 were observed after exposure to 1.8 Gy. Conversely, increased expressions of p53 (5/10 patients; P=0.0239), ERCC1 (5/10 patients; P=0.0294) and EGFR (4/10 patients; P=0.1773) were observed in malignant tissues after radiotherapy with the same radiation dose. TP53 mutations were found only in one patient. Here we show that a single dose of radiotherapy induced EGFR, ERCC1 and p53 expression in malignant tissues from cervical cancer patients but not in cancer cell lines, highlighting the gap between in vitro and in vivo experimental models. Studies on larger patient cohorts are needed to allow an interpretation that an upregulation of p53, EGFR and ERCC1 may be part of a radioresistance mechanism.