EXPRESSION OF AN ALTERNATIVELY SPLICED ERCC1 MESSENGER-RNA SPECIES, IS RELATED TO REDUCED DNA-REPAIR EFFICIENCY IN HUMAN T-LYMPHOCYTES

  • Authors:
    • M DABHOLKAR
    • J VIONNET
    • RJ PARKER
    • F BOSTICKBRUTON
    • A DOBBINS
    • E REED
  • View Affiliations

  • Published online on: March 1, 1995     https://doi.org/10.3892/or.2.2.209
  • Pages: 209-214
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

We have previously shown that in non-drug-selected human T lymphocytes, DNA repair is the primary determinant of cellular resistance to cisplatin (1). In this system, we have assessed mRNA levels of expression of the nucleotide excision repair (NER) genes ERCC1 and XPA, as well as the alternatively spliced species of ERCC1 which lacks exon VIII. The focus of these studies, was to try to identify the possible relative roles of normal XPA, full-length ERCC1, and alternatively spliced ERCC1, in a system where DNA repair is a clear determinant of cisplatin resistance. ERCC1 expression was directly related to cisplatin-DNA adduct repair capability, as well as directly related to cisplatin resistance, suggesting a primary role for ERCC1 in effecting DNA repair. XPA expression was approximately equivalent in each cell line, regardless of the level of DNA repair activity, suggesting a helper role for the product of this gene. The mRNA levels of the alternatively spliced species of ERCC1 were strongly inversely related to DNA repair activity, suggesting a possible inhibitory influence on the DNA repair process. This interpretation is consistent with alternative splicing of several known oncogenes, where the alternatively spliced species has an inhibitory effect on the full-length gene product. The NER pathway appears to be vitally important in effecting cisplatin resistance in non-drug-selected T lymphocytes. Further, it appears that NER may have at least one inhibitory regulatory component.

Related Articles

Journal Cover

March 1995
Volume 2 Issue 2

Print ISSN: 1021-335X
Online ISSN:1791-2431

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
DABHOLKAR M, VIONNET J, PARKER R, BOSTICKBRUTON F, DOBBINS A and REED E: EXPRESSION OF AN ALTERNATIVELY SPLICED ERCC1 MESSENGER-RNA SPECIES, IS RELATED TO REDUCED DNA-REPAIR EFFICIENCY IN HUMAN T-LYMPHOCYTES. Oncol Rep 2: 209-214, 1995
APA
DABHOLKAR, M., VIONNET, J., PARKER, R., BOSTICKBRUTON, F., DOBBINS, A., & REED, E. (1995). EXPRESSION OF AN ALTERNATIVELY SPLICED ERCC1 MESSENGER-RNA SPECIES, IS RELATED TO REDUCED DNA-REPAIR EFFICIENCY IN HUMAN T-LYMPHOCYTES. Oncology Reports, 2, 209-214. https://doi.org/10.3892/or.2.2.209
MLA
DABHOLKAR, M., VIONNET, J., PARKER, R., BOSTICKBRUTON, F., DOBBINS, A., REED, E."EXPRESSION OF AN ALTERNATIVELY SPLICED ERCC1 MESSENGER-RNA SPECIES, IS RELATED TO REDUCED DNA-REPAIR EFFICIENCY IN HUMAN T-LYMPHOCYTES". Oncology Reports 2.2 (1995): 209-214.
Chicago
DABHOLKAR, M., VIONNET, J., PARKER, R., BOSTICKBRUTON, F., DOBBINS, A., REED, E."EXPRESSION OF AN ALTERNATIVELY SPLICED ERCC1 MESSENGER-RNA SPECIES, IS RELATED TO REDUCED DNA-REPAIR EFFICIENCY IN HUMAN T-LYMPHOCYTES". Oncology Reports 2, no. 2 (1995): 209-214. https://doi.org/10.3892/or.2.2.209