Astrocyte-elevated gene-1 confers resistance to pemetrexed in non-small cell lung cancer by upregulating thymidylate synthase expression.
Astrocyte-elevated gene-1 confers resistance to pemetrexed in non-small cell lung cancer by upregulating thymidylate synthase expression.
复制标题
DOI：
10.18632/oncotarget.18717
复制
发表时间：
2017-09-22
期刊：
影响因子：
--
通讯作者：
Yang PC
中科院分区：
文献类型：
--
作者：
Chen CY;Chen YY;Chen JJW;Chen KY;Ho CC;Shih JY;Chang YL;Yu CJ;Yang PC
以往的研究表明，星形胶质细胞升高的基因-1（AEG-1）有助于对各种化疗药物的耐药机制。在这项研究中，我们研究了AEG-1表达水平是否与胸苷酸合成酶（TS）的表达水平相关，因为已知TS的高表达与晚期肺腺癌患者对培美曲塞化疗的耐药性相关。使用培美曲塞耐药肺腺癌PC-9细胞系，我们证明AEG-1 siRNA转染降低TS表达并降低培美曲塞IC 50值。相反，AEG-1过表达与TS表达增加和培美曲塞IC 50值升高相关。临床活检标本的免疫组化染色显示，AEG-1表达较低的患者总体生存时间较长。此外，对重复活检样本的分析显示，TS水平从基线到疾病进展的增加与AEG-1表达的升高显著相关。总之，我们的数据表明TS表达可能受到AEG-1的调节，这些蛋白表达的增加有助于肺癌疾病进展，并可能与培美曲塞耐药的发展有关。
Previous studies have suggested that astrocyte-elevated gene-1 (AEG-1) contributes to the mechanisms of resistance to various chemotherapeutics. In this study, we investigated whether AEG-1 expression level correlated with that of thymidylate synthase (TS), as higher TS expression is known to be associated with the resistance to pemetrexed chemotherapy in patients with advanced lung adenocarcinoma. Using pemetrexed-resistant lung adenocarcinoma PC-9 cell line, we demonstrated that transfection of AEG-1 siRNA lowered TS expression and decreased pemetrexed IC50 value. In contrast, overexpression of AEG-1 was associated with increased expression of TS and higher pemetrexed IC50 value. Immunohistochemical staining of clinical biopsy samples showed that patients with lower AEG-1 expression had longer overall survival time. Moreover, analysis of repeated biopsy samples revealed that an increase in the TS level from baseline to disease progression was significantly associated with the elevation of AEG-1 expression. In conclusion, our data demonstrated that TS expression might be regulated by AEG-1 and that increased expression of these proteins contributes to lung cancer disease progression and may be associated with the development of resistance to pemetrexed.
登录
查看更多内容
影响因子：
50.3
作者：
Hu G;Chong RA;Yang Q;Wei Y;Blanco MA;Li F;Reiss M;Au JL;Haffty BG;Kang Y
通讯作者：
Kang Y
影响因子：
8.4
作者：
Eisenhauer, E. A.;Therasse, P.;Verweij, J.
通讯作者：
Verweij, J.
B7-H3 通过 PI3k-Akt 途径增加胸苷酸合酶表达
影响因子：
--
作者：
Jiang, Bo;Liu, Fen;Hua, Dong
通讯作者：
Hua, Dong
影响因子：
45.3
作者：
Scagliotti, Giorgio Vittorio;Parikh, Purvish;Gandara, David
通讯作者：
Gandara, David
影响因子：
45.3
作者：
Masters, Gregory A.;Temin, Sarah;Johnson, David H.
通讯作者：
Johnson, David H.