Gene expression profiles with cDNA microarray reveal RhoGDI as a predictive marker for paclitaxel resistance in ovarian cancers

Oncol Rep. 2006 May;15(5):1265-71.

Abstract

In the current study, we identified paclitaxel-resistant related genes by comparing gene expression profiles of paclitaxel-resistant and parent ovarian cancer cell lines. Gene expression profiles of the human ovarian cancer cell line (KF28), cisplatin-resistant cell line (KFr13) induced from KF28, and paclitaxel-resistant cell lines (KF28TX and KFr13TX) induced by exposing KF28 and KFr13 to dose-escalating paclitaxel were compared and analyzed using cDNA microarray. Of 557 human cancer-related cDNA transcripts compared, 5 genes were found to be underexpressed and 5 genes overexpressed in the paclitaxel-resistant KF28TX, while another paclitaxel-resistant KFr13TX had 5 underexpressed and 8 overexpressed genes. Among these genes, overexpression of the ATP-binding cassette subfamily (MDR-1), Rho guanine dinucleotide phosphate dissociation inhibitor beta (RhoGDI) and insulin-like growth factor binding protein 3 (IGFBP-3) was observed in both paclitaxel-resistant cell lines. Using real-time quantitative PCR, we confirmed the array results. We therefore conclude that IGFBP-3, RhoGDI and MDR-1 were correlated with paclitaxel resistance. Moreover, immunohistochemical staining was analyzed in 22 serous ovarian cancer tissues from patients who received paclitaxel-based chemotherapy, and RhoGDI overexpression was observed more frequently in non-responsers than in responders (p=0.004). RhoGDI expression proved to be a predictive marker of paclitaxel resistance not only in paclitaxel-resistant cell lines, but also in clinical samples.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • Antineoplastic Agents, Phytogenic / therapeutic use*
  • Biomarkers, Tumor / genetics*
  • Cystadenocarcinoma, Serous / drug therapy
  • Cystadenocarcinoma, Serous / genetics
  • Cystadenocarcinoma, Serous / pathology
  • Drug Resistance, Neoplasm / genetics*
  • Female
  • Gene Expression Profiling*
  • Gene Expression Regulation, Neoplastic
  • Guanine Nucleotide Dissociation Inhibitors / genetics*
  • Humans
  • Insulin-Like Growth Factor Binding Protein 3 / genetics
  • Insulin-Like Growth Factor Binding Protein 3 / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / pathology
  • Paclitaxel / therapeutic use*
  • Tumor Cells, Cultured
  • rho Guanine Nucleotide Dissociation Inhibitor alpha
  • rho-Specific Guanine Nucleotide Dissociation Inhibitors

Substances

  • ARHGDIA protein, human
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antineoplastic Agents, Phytogenic
  • Biomarkers, Tumor
  • Guanine Nucleotide Dissociation Inhibitors
  • Insulin-Like Growth Factor Binding Protein 3
  • rho Guanine Nucleotide Dissociation Inhibitor alpha
  • rho-Specific Guanine Nucleotide Dissociation Inhibitors
  • Paclitaxel