Hypermethylation of growth arrest DNA-damage-inducible gene 45 in non-small cell lung cancer and its relationship with clinicopathologic features

Molecules and Cells
Yeon Kyung NaDong Sun Kim

Abstract

The growth arrest DNA-damage-inducible protein 45 (GADD45) can serve as a key coordinator of the stress response by regulating cell cycle progression, genomic stability, DNA repair, and other stress-related responses. Although deregulation of GADD45 expression has been reported in several types of human tumors, its role in lung cancer is still unknown. DNA hypermethylation of promoter CpG islands is known to be a major mechanism for epigenetic inactivation of tumor suppressor genes. We investigated the methylation status of GADD45 family genes (GADD45A, B, and G) in 139 patients with non-small cell lung cancer (NSCLC) using methylation-specific PCR (MSP) and correlated the results with clinicopathologic features of the patients. Methylation frequencies in tumors were 1.4% for GADD45A, 7.2% for GADD45B, and 31.6% for GADD45G. RT-PCR and MSP analysis showed that promoter methylation of the GADD45G gene resulted in downregulation of its mRNA expression. GADD45G methylation was significantly more frequent in female patients than male patients (P = 0.035). This finding suggests that methylation-associated down-regulation of the GADD45G gene may be involved in lung tumorigenesis.

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Citations

Dec 14, 2011·Critical Reviews in Oncogenesis·Dan A LiebermannBarbara Hoffman
Oct 12, 2011·Ageing Research Reviews·Alexey A MoskalevVadim E Fraifeld
Apr 26, 2013·International Journal of Cancer. Journal International Du Cancer·Wei GuoZhibin Yang
Aug 14, 2013·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Jung-Hwan KimFrank J Gonzalez
May 29, 2016·Biochemical and Biophysical Research Communications·Jung-Hwan KimFrank J Gonzalez
Jun 6, 2012·International Journal of Oncology·Ahmed KhamasKenichi Sugihara
May 30, 2014·Experimental Biology and Medicine·Li ZhangYongzhong Liu
Aug 17, 2012·Molecular Medicine Reports·Xiangrui MengQingxia Fan
Oct 27, 2011·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Ping YangWen Chen

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