Abstract
Human ovarian cancer cells and tissues were examined for the presence or absence of a 42-bp splicing variant of ERCC1 gene, and for a possible functional role of this 42-bp sequence. This specific sequence exists in exon I, the 5′-UTR of the gene. Loss of this 42-bp sequence was associated with increased ERCC1 mRNA expression, in an assessment of 121 ovarian cancer specimens (p2<10−6). In cells in tissue culture, the absence of the 42-bp segment was associated with a twofold increased ability to drive transcription in a Luciferase reporter system. Protein can be demonstrated in ovarian cancer cells based on EMSA analysis. Computer analysis shows that this 42-bp sequence contains several binding sites, including a core-binding domain for protein RFX1, transcriptional repressor. These preliminary results lay the groundwork in determination of potential roles for a negative regulatory element in NER repair pathway.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Behrens BC, Hamilton TC, Masuda H, Grotzinger KR, Whang-Peng J, Louie KG, Knutsen T, McKoy WM, Young RC, Ozols RF . 1987 Cancer Res. 47: 414–418
Bonovich M, Cross C, Reed E, Vinson C . 2000 Proc. Am. Assoc. Cancer Res. 41: 399
Dabholkar M, Vionnet JA, Bostick-Bruton F, Yu JJ, Reed E . 1994 J. Clin. Invest. 94: 703–708
Digman JD, Lebovitz RM, Roeder RG . 1983 Nucleic Acid Res. 11: 1475–1489
Li Q, Gardner K, Zhang L, Tsang B, Bostick-Bruton F, Reed E . 1998 J. Biol. Chem. 273: 23419–23425
Metzger R, Leichman CG, Danenberg KD, Danenberg PV, Lenz HJ, Hayashi K, Groshen S, Salonga D, Cohen H, Laine L, Crookes P, Silberman H, Baranda J, Konda B, Leichman L . 1998 J. Clin. Oncol. 16: 309–316
Mu D, Hsu DS, Sancar A . 1996 J. Biol. Chem. 271: 8285–8294
Palmiter RD . 1974 Biochemistry 13: 3606–3615
Parker RJ, Eastman A, Bostick-Bruton F, Reed E . 1991 J. Clin. Invest. 87: 772–777
Quandt K, Frech K, Karas H, Wingender E, Werner T . 1995 Nucleic Acids Res. 23: 4878–4884
Reed E . 1998 Cancer Treat. Rev. 24: 331–344
Sancar A . 1994 Science 266: 1954–1956
Van Duin M, de Wit J, Odijk H, Westerveld A, Yasui A, Koken HM, Hoeijmakers JH, Bootsma D . 1986 Cell 44: 913–923
Van Vuuren AJ, Appeldoorn E, Odijk H, Humbert S, Moncollin V, Eker AP, Jaspers NG, Egly JM, Hoeijmakers JH . 1995 Mutation Res. 337: 25–39
Yang LY, Li L, Jiang H, Shen Y, Plunkett W . 2000 Clin. Cancer Res. 6: 773–781
Acknowledgements
Dr Gregory S Leppert provided valuable comments in the development of this article. This work was supported in part by the ORMH, NIH, Bethesda, Maryland, USA.
Accession number
The cDNA sequence was deposited in the EMBL database under Accession number AF433652.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Yu, J., Thornton, K., Guo, Y. et al. An ERCC1 splicing variant involving the 5′-UTR of the mRNA may have a transcriptional modulatory function. Oncogene 20, 7694–7698 (2001). https://doi.org/10.1038/sj.onc.1204977
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1204977
