Overexpression and hypomethylation of Flap endonuclease 1 gene in breast and other cancers

Purnima Singh, Ming Yang, Huifang Dai, Dianke Yu, Qin Huang, Wen Tan, Kemp H. Kernstine, Dongxin Lin, Binghui Shen

Research output: Contribution to journalArticle

71 Scopus citations

Abstract

Flap endonuclease 1 (FEN1) is a structure-specific nuclease best known for its critical roles in Okazaki fragment maturation, DNA repair, and apoptosis-induced DNA fragmentation. Functional deficiencies in FEN1, in the forms of somatic mutations and polymorphisms, have recently been shown to lead to autoimmunity, chronic inflammation, and predisposition to and progression of cancer. To explore how FEN1 contributes to cancer progression, we examined FEN1 expression using 241 matched pairs of cancer and corresponding normal tissues on a gene expression profiling array and validated differential expression by quantitative real-time PCR and immunohistochemistry. Furthermore, we defined the minimum promoter of human FEN1 and examined the methylation statuses of the 5′ region of the gene in paired breast cancer tissues. We show that FEN1 is significantly up-regulated in multiple cancers and the aberrant expression of FEN1 is associated with hypomethylation of the CpG island within the FEN1 promoter in tumor cells. The overexpression and promoter hypomethylation of FEN1 may serve as biomarkers for monitoring the progression of cancers.

Original languageEnglish (US)
Pages (from-to)1710-1717
Number of pages8
JournalMolecular Cancer Research
Volume6
Issue number11
DOIs
StatePublished - Nov 1 2008

ASJC Scopus subject areas

  • Molecular Biology
  • Oncology
  • Cancer Research

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