Overexpression and hypomethylation of flap endonuclease 1 gene in breast and other cancers.
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.
Singh
Purnima
P
Department of Radiation Biology, City of Hope National Medical Center and Beckman Research Institute, Duarte, California 91010, USA.
Yang
Ming
M
Dai
Huifang
H
Yu
Dianke
D
Huang
Qin
Q
Tan
Wen
W
Kernstine
Kemp H
KH
Lin
Dongxin
D
Shen
Binghui
B
D001940:Breast / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D018899:CpG Islands; D019175:DNA Methylation; D018450:Disease Progression; D005260:Female; D045585:Flap Endonucleases / Q000235:genetics*; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis
D045585:Flap Endonucleases; C468317:FEN1 protein, human