Gene expression profiles in the cellular response to a multinuclear platinum complexe

被引:9
作者
Gatti, L [1 ]
Beretta, GL [1 ]
Carenini, N [1 ]
Corna, E [1 ]
Zunino, F [1 ]
Perego, P [1 ]
机构
[1] Ist Nazl Tumori, I-20133 Milan, Italy
关键词
platinum compound; sensitivity; resistance; gene expression; cDNA array;
D O I
10.1007/s00018-003-4024-5
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 15genes including cell cycle and growth regulators, tumor suppressors and signal transduction genes. In cisplatin-resistant A431/Pt cells, BBR3464increased the expression of 15genes 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.
引用
收藏
页码:973 / 981
页数:9
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