Confirmation of 42-bp deletion within the ERCC1 5' UTR.

  • Authors:
    • Tiyuan Li
    • Yuping Song
    • Xiaobing Liang
    • Ying Guo
    • Eddie Reed
    • Jing Jie Yu
  • View Affiliations

  • Published online on: October 1, 2004     https://doi.org/10.3892/ijo.25.4.1105
  • Pages: 1105-1116
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Abstract

Our previous studies revealed a splicing variant (lacking a 42 base pair segment) within the 5'-UTR of the ERCC1 gene, a critical component of the nucleotide excision repair (NER) pathway that plays an important role in the development of chemoresistance in platinum-based anticancer therapy. This 42-bp segment seems to possess a regulatory function in ERCC1 expression and representing the level of clinical response to platinum-treatment in ovarian cancer patients. To confirm the existence of the 42-bp deletion and to investigate the 42-bp function, we performed several experiments and assays. Northern blot analysis and RNase protection assay provide evidence that the 42-bp deletion occurs at RNA level of ERCC1 5'-UTR in both ovarian cancer cell lines and ovarian cancer tissues. Luciferase assay suggests that this gene fragment possesses a regulatory function as an enhancer of ERCC1 gene expression in ovarian cancer cells. In Electrophoretic Mobility Shift Assay (EMSA), a shift band present in the ovarian cancer cell line extracts is consistent with the presence of an intracellular protein that recognizes this specific 42-bp sequence. Further, specific EMSA results with 42-bp probe mutated at the site of RFX-1 indicate different putative-DNA binding proteins, rather than RFX-1. We conclude that the 42-bp sequence within the 5'-UTR influences the expression of ERCC1 and hence can influence response to cisplatin in ovarian cancer therapy.

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October 2004
Volume 25 Issue 4

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

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APA
Li, T., Song, Y., Liang, X., Guo, Y., Reed, E., & Yu, J. (2004). Confirmation of 42-bp deletion within the ERCC1 5' UTR.. International Journal of Oncology, 25, 1105-1116. https://doi.org/10.3892/ijo.25.4.1105
MLA
Li, T., Song, Y., Liang, X., Guo, Y., Reed, E., Yu, J."Confirmation of 42-bp deletion within the ERCC1 5' UTR.". International Journal of Oncology 25.4 (2004): 1105-1116.
Chicago
Li, T., Song, Y., Liang, X., Guo, Y., Reed, E., Yu, J."Confirmation of 42-bp deletion within the ERCC1 5' UTR.". International Journal of Oncology 25, no. 4 (2004): 1105-1116. https://doi.org/10.3892/ijo.25.4.1105