Gene expression profiles in the cellular response to a multinuclear platinum complex.
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.
Gatti
L
L
Istituto Nazionale Tumori, Via Venezian 1, 20133 Milan, Italy.
Beretta
G L
GL
Carenini
N
N
Corna
E
E
Zunino
F
F
Perego
P
P
D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D009944:Organoplatinum Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy*
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D012333:RNA, Messenger; C114062:BBR 3464