Genome-wide transcriptional analysis of carboplatin response in chemosensitive and chemoresistant ovarian cancer cells.
We have recently described an ex vivo chemoresponse assay for determining chemosensitivity in primary cultures of human tumors. In this study, we have extended these experiments in an effort to correlate chemoresponse data with gene expression patterns at the level of transcription. Primary cultures of cells derived from ovarian carcinomas of individual patients (n=6) were characterized using the ChemoFx assay and classified as either carboplatin sensitive (n=3) or resistant (n=3). Three representative cultures of cells from each individual tumor were then subjected to Affymetrix gene chip analysis (n=18) using U95A human gene chip arrays. Data were analyzed using the dCHIP software package. We identified a significant number of genes whose expression patterns were altered between carboplatin chemosensitive and chemoresistant cells, in normal culture conditions and in the presence of carboplatin for either 2 or 72 hours. Among these differentially expressed genes, we found a significant proportion to be associated with apoptosis, cell-cell communication, cell adhesion, DNA repair, and cell proliferation. In general, the molecular phenotype displayed by chemoresistant cells was reflective of an extended life span in culture in the presence of carboplatin and the genes that define this phenotype are potential biomarkers for the prognostic management of ovarian cancer patients.
Peters
David
D
Department of Pharmacology and Therapeutics, University of Liverpool, The Sherrington Buildings, Ashton Street, Liverpool, L69 3GE United Kingdom. david.peters@mail.hgen.pitt.edu
Freund
John
J
Ochs
Robert L
RL
D000970:Antineoplastic Agents / Q000494:pharmacology*; D016190:Carboplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects* / Q000235:genetics; D015894:Genome, Human; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics
D000970:Antineoplastic Agents; D016190:Carboplatin