Cellular resistance to mitomycin C is associated with overexpression of MDR-1 in a urothelial cancer cell line (MGH-U1)
Hayes, M.C., Birch, B.R., Cooper, A.J. and Primrose, J.N. (2001) Cellular resistance to mitomycin C is associated with overexpression of MDR-1 in a urothelial cancer cell line (MGH-U1). BJU International, 87, (3), 245-250. (doi:10.1046/j.1464-410x.2001.02027.x).
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Description/Abstract
Objective: to compare multidrug resistance (MDR)-1 and MDR-3 gene expression in a new urothelial cancer cell line (MGHU-1, with resistance to mitomycin C) against controls and the established (epirubicin-resistant) MDR clone, and to correlate MDR with cytotoxicity data.
Materials and methods: resistance to mitomycin C was induced by the long-term exposure of wild-type MGHU-1 cells to increasing concentrations (20–400 nmol/L) of mitomycin C. The cytotoxicity of mitomycin C or epirubicin was then compared in MGHU-1, MGHU-MMC (mitomycin C-resistant) and MGHU-1R (established MDR) cells, using the tetrazolium biomass assay. The expression of MDR-1 and -3 was investigated by the reverse transcriptase-polymerase chain reaction, using cDNA-specific primers after titration, and compared with DNA and negative controls.
Results: MDR-1 and -3 were significantly and equally overexpressed in MGHU-1R, and associated with a dramatic increase in the 50% inhibitory drug concentration (P < 0.001) for mitomycin C and epirubicin against controls. In MGHU-MMC, the overexpression of MDR-1 was three times greater than that of MDR-3. The cytotoxicity profile for both agents was very similar to that of MGHU-1R. Trace amounts of MDR-1, but not MDR-3, were identified in the MGHU-1 wild-type.
Conclusions: Urothelial cancer cell resistance to mitomycin C is associated with cross-resistance to epirubicin and overexpression of MDR-1, suggesting that mitomycin C falls within the MDR category. Clinical application of this methodology may allow patients to be identified who are unlikely to benefit from intravesical chemotherapy.
| Item Type: | Article |
|---|---|
| Related URLs: | |
| Subjects: | R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) Q Science > QH Natural history > QH426 Genetics |
| Divisions: | University Structure - Pre August 2011 > School of Medicine > Cancer Sciences |
| Item ID: | 26379 |
| Date Deposited: | 24 Apr 2006 |
| Last Modified: | 01 Jun 2011 08:50 |
| Contributors: | Hayes, M.C. (Author) Birch, B.R. (Author) Cooper, A.J. (Author) Primrose, J.N. (Author) |
| Date: | 2001 |
| Status: | Published |
| Contact Email Address: | jnp1@soton.ac.uk |
| URI: | http://eprints.soton.ac.uk/id/eprint/26379 |
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