Disruption of the Fanconi anemia-BRCA pathway in cisplatin-sensitive ovarian tumors - PubMed (original) (raw)

doi: 10.1038/nm852. Epub 2003 Apr 7.

Affiliations

• PMID: 12692539
• DOI: 10.1038/nm852

Disruption of the Fanconi anemia-BRCA pathway in cisplatin-sensitive ovarian tumors

Toshiyasu Taniguchi et al. Nat Med. 2003 May.

Abstract

Ovarian tumor cells are often genomically unstable and hypersensitive to cisplatin. To understand the molecular basis for this phenotype, we examined the integrity of the Fanconi anemia-BRCA (FANC-BRCA) pathway in those cells. This pathway regulates cisplatin sensitivity and is governed by the coordinate activity of six genes associated with Fanconi anemia (FANCA, FANCC, FANCD2, FANCE, FANCF and FANCG) as well as BRCA1 and BRCA2 (FANCD1). Here we show that the FANC-BRCA pathway is disrupted in a subset of ovarian tumor lines. Mono-ubiquitination of FANCD2, a measure of the function of this pathway, and cisplatin resistance were restored by functional complementation with FANCF, a gene that is upstream in this pathway. FANCF inactivation in ovarian tumors resulted from methylation of its CpG island, and acquired cisplatin resistance correlated with demethylation of FANCF. We propose a model for ovarian tumor progression in which the initial methylation of FANCF is followed by FANCF demethylation and ultimately results in cisplatin resistance.

PubMed Disclaimer

Comment in

• Cisplatin and the sensitive cell.
  Bagby GC, Olson SB. Bagby GC, et al. Nat Med. 2003 May;9(5):513-4. doi: 10.1038/nm0503-513. Nat Med. 2003. PMID: 12724761 No abstract available.

Similar articles

• Variation in cisplatinum sensitivity is not associated with Fanconi Anemia/BRCA pathway inactivation in head and neck squamous cell carcinoma cell lines.
  Snyder ER, Ricker JL, Chen Z, Waes CV. Snyder ER, et al. Cancer Lett. 2007 Jan 8;245(1-2):75-80. doi: 10.1016/j.canlet.2005.12.028. Epub 2006 Feb 7. Cancer Lett. 2007. PMID: 16466850
• Disruption of the FA/BRCA pathway in bladder cancer.
  Neveling K, Kalb R, Florl AR, Herterich S, Friedl R, Hoehn H, Hader C, Hartmann FH, Nanda I, Steinlein C, Schmid M, Tonnies H, Hurst CD, Knowles MA, Hanenberg H, Schulz WA, Schindler D. Neveling K, et al. Cytogenet Genome Res. 2007;118(2-4):166-76. doi: 10.1159/000108297. Cytogenet Genome Res. 2007. PMID: 18000367
• Cisplatin and the sensitive cell.
  Bagby GC, Olson SB. Bagby GC, et al. Nat Med. 2003 May;9(5):513-4. doi: 10.1038/nm0503-513. Nat Med. 2003. PMID: 12724761 No abstract available.
• The Fanconi Anemia/BRCA signaling pathway: disruption in cisplatin-sensitive ovarian cancers.
  D'Andrea AD. D'Andrea AD. Cell Cycle. 2003 Jul-Aug;2(4):290-2. Cell Cycle. 2003. PMID: 12851475 Review.
• FANCF methylation contributes to chemoselectivity in ovarian cancer.
  Olopade OI, Wei M. Olopade OI, et al. Cancer Cell. 2003 May;3(5):417-20. doi: 10.1016/s1535-6108(03)00111-9. Cancer Cell. 2003. PMID: 12781358 Review.

Cited by

• RNA interference-mediated FANCF silencing sensitizes OVCAR3 ovarian cancer cells to adriamycin through increased adriamycin-induced apoptosis dependent on JNK activation.
  He M, Sun HG, Hao JY, Li YL, Yu JK, Yan YY, Zhao L, Li N, Wang Y, Bai XF, Yu ZJ, Zheng ZH, Mi XY, Wang EH, Wei MJ. He M, et al. Oncol Rep. 2013 May;29(5):1721-9. doi: 10.3892/or.2013.2295. Epub 2013 Feb 21. Oncol Rep. 2013. PMID: 23440494 Free PMC article.
• Components of a Fanconi-like pathway control Pso2-independent DNA interstrand crosslink repair in yeast.
  Ward TA, Dudášová Z, Sarkar S, Bhide MR, Vlasáková D, Chovanec M, McHugh PJ. Ward TA, et al. PLoS Genet. 2012;8(8):e1002884. doi: 10.1371/journal.pgen.1002884. Epub 2012 Aug 9. PLoS Genet. 2012. PMID: 22912599 Free PMC article.
• Estrogen receptor alpha, BRCA1, and FANCF promoter methylation occur in distinct subsets of sporadic breast cancers.
  Wei M, Xu J, Dignam J, Nanda R, Sveen L, Fackenthal J, Grushko TA, Olopade OI. Wei M, et al. Breast Cancer Res Treat. 2008 Sep;111(1):113-20. doi: 10.1007/s10549-007-9766-6. Epub 2007 Oct 12. Breast Cancer Res Treat. 2008. PMID: 17932744 Free PMC article.
• Combination therapy with atorvastatin and celecoxib delays tumor formation in a Fanconi anemia mouse model.
  Zhang QS, Deater M, Phan N, Marcogliese A, Major A, Guinan EC, Grompe M. Zhang QS, et al. Pediatr Blood Cancer. 2019 Jan;66(1):e27460. doi: 10.1002/pbc.27460. Epub 2018 Sep 25. Pediatr Blood Cancer. 2019. PMID: 30255556 Free PMC article.
• Clinical relevance of the homologous recombination machinery in cancer therapy.
  Miyagawa K. Miyagawa K. Cancer Sci. 2008 Feb;99(2):187-94. doi: 10.1111/j.1349-7006.2007.00644.x. Epub 2007 Oct 22. Cancer Sci. 2008. PMID: 17953711 Free PMC article. Review.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Nature Publishing Group

• Other Literature Sources

  • The Lens - Patent Citations Database

• Medical

  • MedlinePlus Health Information

• Miscellaneous

  • NCI CPTAC Assay Portal