Expression analysis of genes involved in oxaliplatin response and development of oxaliplatin-resistant HT29 colon cancer cells.
Article Details
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Plasencia C, Martinez-Balibrea E, Martinez-Cardus A, Quinn DI, Abad A, Neamati N
Expression analysis of genes involved in oxaliplatin response and development of oxaliplatin-resistant HT29 colon cancer cells.
Int J Oncol. 2006 Jul;29(1):225-35.
- PubMed ID
- 16773204 [ View in PubMed]
- Abstract
The interrelationship between platinum resistance and clinical response is not well established. The purpose of this study is to evaluate the expression of 14 genes involved in platinum resistance in a colon cancer cell line (HT29) and its oxaliplatin (OXA)-resistant sublines. Resistant cells exhibited lower expression of many of these genes suggesting that several pathways may be implicated in OXA resistance. Particularly, OXA resistance is accompanied by defects in drug uptake (downregulation of the hCTR1 transporter) and enhanced DNA repair (upregulation of the XPD gene). Our data also confirmed that copper transporters and chaperones are involved in OXA resistance in colorectal cancer cells as evidenced by the overexpression of ATP7A and CCS in response to OXA exposure. Moreover, increased CCS expression suggests a role for SOD1 in OXA detoxification. Whereas exposure to OXA in HT29 induced significant changes in expression of many of the genes analyzed, only ATP7A, XPD and SRPK1 gene expression was increased in OXA-treated HTOXAR3 resistant cells. To our knowledge, this is the first report of implicating SRPK1 in OXA resistance. This study provides the basis for further evaluation of these putative markers of OXA response and resistance in colorectal cancer patients who are candidates for treatment with OXA.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Oxaliplatin Superoxide dismutase [Cu-Zn] Protein Humans NoSubstrateDetails - Pharmaco-transcriptomics
Drug Drug Groups Gene Gene ID Change Interaction Chromosome Oxaliplatin Approved Investigational ATP7A 538 upregulated oxaliplatin results in increased expression of ATP7A mRNA Xq21.1 Oxaliplatin Approved Investigational ATP7B 540 downregulated oxaliplatin results in decreased expression of ATP7B mRNA 13q14.3 Oxaliplatin Approved Investigational CCS 9973 upregulated oxaliplatin results in increased expression of CCS mRNA 11q13.2 Oxaliplatin Approved Investigational ERCC1 2067 upregulated oxaliplatin results in increased expression of ERCC1 mRNA 19q13.32 Oxaliplatin Approved Investigational ERCC2 2068 upregulated oxaliplatin results in increased expression of ERCC2 mRNA 19q13.32 Oxaliplatin Approved Investigational GSTP1 2950 upregulated oxaliplatin results in increased expression of GSTP1 mRNA 11q13.2 Oxaliplatin Approved Investigational MT2A 4502 downregulated oxaliplatin results in decreased expression of MT2A mRNA 16q13 Oxaliplatin Approved Investigational SRPK1 6732 upregulated oxaliplatin results in increased expression of SRPK1 mRNA 6p21.31