Gatti L, Beretta G L, Carenini N, Corna E, Zunino F, Perego P
Istituto Nazionale Tumori, Via Venezian 1, 20133 Milan, Italy.
Cell Mol Life Sci. 2004 Apr;61(7-8):973-81. doi: 10.1007/s00018-003-4024-5.
We used cDNA arrays to monitor modulation of mRNA expression after exposure to a multinuclear platinum complex (BBR3464) in a human cervix squamous cell carcinoma cell line (A431) and in a cisplatin-resistant subline (A431/Pt) exhibiting collateral sensitivity to BBR3464. In parental A431cells, the drug induced at least twofold up-regulation of 15 genes including cell cycle and growth regulators, tumor suppressors and signal transduction genes. In cisplatin-resistant A431/Pt cells, BBR3464increased the expression of 15 genes such as apoptosis regulators and genes involved in the DNA damage response. Interestingly, BBR3464induced up-regulation of anti-metastatic factors together with down-regulation of several pro-metastatic factors. Cell cycle analysis indicated a marked G2arrest in treated A431cells, whereas an apoptotic response was documented in A431/Pt cells. These differential patterns of transcriptional profile in sensitive and resistant cells are consistent with a role for cell cycle regulation in the response to BBR3464.
我们使用cDNA阵列来监测在人宫颈鳞状细胞癌细胞系（A431）和对BBR3464表现出协同敏感性的顺铂耐药亚系（A431/Pt）中，暴露于多核铂配合物（BBR3464）后mRNA表达的调节情况。在亲本A431细胞中，该药物诱导了15个基因至少两倍的上调，这些基因包括细胞周期和生长调节因子、肿瘤抑制因子以及信号转导基因。在顺铂耐药的A431/Pt细胞中，BBR3464增加了15个基因的表达，如凋亡调节因子和参与DNA损伤反应的基因。有趣的是，BBR3464诱导了抗转移因子的上调以及几种促转移因子的下调。细胞周期分析表明，处理后的A431细胞出现明显的G2期阻滞，而A431/Pt细胞有凋亡反应记录。敏感和耐药细胞中这些转录谱的差异模式与细胞周期调节在对BBR3464反应中的作用一致。
