TY - JOUR
T1 - Overexpression and hypomethylation of Flap endonuclease 1 gene in breast and other cancers
AU - Singh, Purnima
AU - Yang, Ming
AU - Dai, Huifang
AU - Yu, Dianke
AU - Huang, Qin
AU - Tan, Wen
AU - Kernstine, Kemp H.
AU - Lin, Dongxin
AU - Shen, Binghui
PY - 2008/11/1
Y1 - 2008/11/1
N2 - 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.
AB - 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.
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U2 - 10.1158/1541-7786.MCR-08-0269
DO - 10.1158/1541-7786.MCR-08-0269
M3 - Article
C2 - 19010819
AN - SCOPUS:56449116122
SN - 1541-7786
VL - 6
SP - 1710
EP - 1717
JO - Molecular Cancer Research
JF - Molecular Cancer Research
IS - 11
ER -