Semi-quantitative detection of GADD45-gamma methylation levels in gastric, colorectal and pancreatic cancers using methylation-sensitive high-resolution melting analysis

Abstract

In summary, application of HRM analysis to large amount of clinical samples proves to be a fast and high-throughput way to investigate the epigenetic status of GADD45G. And this is the first study to evaluate the prevalence of GADD45G methylation based on large amount of tumor samples, showing that epigenetic regulation of GADD45G was associated with carcinogenesis.

Methylation‐mediated repression of GADD45A and GADD45G expression in gastric cardia adenocarcinoma

“…37 These data indicate that GADD45A may play different roles in different carcinomas. The fact that GCA tumor tissues showed decreased mRNA and protein expression of GADD45G which we have found in this study was consistent with the experiments from several laboratories which have demonstrated a marked decrease in GADD45G expression in pituitary adenomas, 16 anaplastic thyroid cancer, 18 gastric cancer, colorectal cancer, pancreatic cancer, 19 non-Hodgkin's lymphoma, Hodgkin's lymphoma, nasopharyngeal carcinoma, cervical carcinoma, esophageal carcinoma, and lung carcinoma. 12 Consistent with a role for GADD45G in negative growth regulation, Zhang et al 20 showed that transfection of GADD45G cDNA, in pituitary-derived cell lines, resulted in a substantial growth reduction in colony-forming assays.…”

“…[12][13][14][15][16] It has been reported that GADD45A is epigenetically repressed and is a potential target for treatment of prostate cancer and breast cancer. 14,17 GADD45B is downregulated in hepatocellular carcinoma through methylation, 15 and GADD45G is also downregulated in anaplastic thyroid cancer, 18 gastric, colorectal, pancreatic cancers, 19 and pituitary adenoma. 20 Even with the potential importance of GADD45 gene family in carcinogenesis, little has been investigated about the role of GADD45 gene family in GCA.…”

GADD45 Proteins: Central Players in Tumorigenesis

“…GADD45γ CpG island methylation is present in 75% of carcinoma and lymphoma cell lines, 85% of non-Hodgkin’s lymphomas, 50% of Hodgkin’s lymphomas, 73% of nasopharyngeal carcinomas, 50% of cervical carcinomas, 29% of esophageal carcinomas, and 40% of lung carcinomas, while no methylation is present in any immortalized normal epithelial cell line, normal tissue, or peripheral blood mononuclear cells [131, 132]. Furthermore, recent findings demonstrated that methylation of the GADD45γ gene is also more frequent in gastric, colorectal and pancreatic cancers cells compared to normal cells [133], and the loss of GADD45γ expression in pituitary tumors is associated with methylation of CpG islands in the GADD45γ gene [134]. …”

Gadd45 proteins: Relevance to aging, longevity and age-related pathologies

“…Thus, this common epigenetic modification could be important in linking cancer and aging. With regard to this notion, the methylation of the Gadd45γ promoter was found to be significantly higher in different types of cancer than in normal tissues (Zhang et al, 2010). Nevertheless, treatment of cancer cells with DNA methyltransferase inhibitors can restore Gadd45β expression to its level in the non-tumorous cells (Qiu et al, 2004).…”