Chromosomal imbalance maps of human 5FU-resistant colorectal cancer cell lines: Implications in the analysis of 5FU-acquired resistance mechanisms

  • Authors:
    • C. Plasencia
    • P. H. Rooney
    • M. Taron
    • E. Martinez-Balibrea
    • H. L. McLeod
    • A. Abad
  • View Affiliations

  • Published online on: May 1, 2003     https://doi.org/10.3892/ijo.22.5.945
  • Pages: 945-953
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Thymidylate synthase (TS), a critical enzyme in the de novo synthesis of thymidylate, is an important target for fluoropyrimidines and folate-based TS inhibitors. Overexpression of TS has been correlated to 5-fluorouracil (5FU)-resistance. Because 5FU still remains a basic component of the treatment of colorectal cancer, circumvention of resistance is of vital importance. A panel of sensitive (HT29 and LoVo) and 5FU-resistant colorectal cancer cell lines (HT29-5FUR and LoVo-5FUR) were subjected to comparative genomic hybridization (CGH) analysis to identify possible amplified/deleted regions associated with 5FU-resistance in colon tumours. We have identified chromosomal gains at 5p, 6, 7p, 7q and 8q and one loss at 3q in 5FU-resistant cells as compared to corresponding sensitive cell lines. Neither chromosomal gains at 18p nor gene amplification of TS were observed in our resistant cell lines although an overexpression of TS gene exists (at mRNA level) in these cell lines as compared with corresponding parental cells. Most of the chromosomal gains identified in this study occur frequently in sporadic colorectal tumours and has been associated to a poor prognosis and a greater progression of the tumour and could be related to a worse chemotherapy response. The chromosomal imbalance profile detected in 5FU-resistant cell lines should provide a basis for interpreting mechanisms of 5FU-resistance in colorectal cancer and also possibly in other tumours treated with this agent. This study also identified new genes potentially implicated in 5FU-resistance and suggests new targets that could be useful for the chemotherapy treatment of colorectal cancer.

Related Articles

Journal Cover

May 2003
Volume 22 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Plasencia C, Rooney PH, Taron M, Martinez-Balibrea E, McLeod HL and Abad A: Chromosomal imbalance maps of human 5FU-resistant colorectal cancer cell lines: Implications in the analysis of 5FU-acquired resistance mechanisms. Int J Oncol 22: 945-953, 2003
APA
Plasencia, C., Rooney, P.H., Taron, M., Martinez-Balibrea, E., McLeod, H.L., & Abad, A. (2003). Chromosomal imbalance maps of human 5FU-resistant colorectal cancer cell lines: Implications in the analysis of 5FU-acquired resistance mechanisms. International Journal of Oncology, 22, 945-953. https://doi.org/10.3892/ijo.22.5.945
MLA
Plasencia, C., Rooney, P. H., Taron, M., Martinez-Balibrea, E., McLeod, H. L., Abad, A."Chromosomal imbalance maps of human 5FU-resistant colorectal cancer cell lines: Implications in the analysis of 5FU-acquired resistance mechanisms". International Journal of Oncology 22.5 (2003): 945-953.
Chicago
Plasencia, C., Rooney, P. H., Taron, M., Martinez-Balibrea, E., McLeod, H. L., Abad, A."Chromosomal imbalance maps of human 5FU-resistant colorectal cancer cell lines: Implications in the analysis of 5FU-acquired resistance mechanisms". International Journal of Oncology 22, no. 5 (2003): 945-953. https://doi.org/10.3892/ijo.22.5.945