Abnormal expression of GADD45B in human colorectal carcinoma

Abstract

BackgroundGADD45B is a member of the growth arrest DNA damage-inducible gene family associated with cell growth control, apoptosis, and DNA damage repair response. The aim of this study is to detect the role of GADD45B in colorectal carcinoma (CRC); the area not studied in depth to date.MethodsThe mRNA and protein levels of GADD45B were examined by Real-Time quantitative PCR (RT-qPCR) and immunohistochemistry (IHC) in CRC tissues and adjacent noncancerous tissues (ANCT). Over-expression plasmids and SiRNA were used to regulate GADD45B expression in CRC cell lines in vitro and flow cytometry and Western blotting were used to detect apoptotic changes.ResultsThe mRNA and protein levels of GADD45B were significantly higher in CRC tissues than those in ANCT (P<0.05). Up-regulation of GADD45B was also correlated with relapse and death of CRC patients (P<0.05). The Kaplan-Meier survival curves indicated that disease-free survival (DFS) was significantly worse in CRC patients who showed GADD45B overexpression. A Cox multivariate analysis revealed that GADD45B overexpression and TNM stage were significant factors affecting patients’ survival. On the other hand, as a tumor suppressor gene, GADD45B amplified from normal colorectal tissues could induce apoptosis in CRC cell lines and may be associated with the p53-mediated apoptotic pathways.ConclusionGADD45B, a tumor suppressor gene potentially through the p53-mediated apoptotic pathways, is paradoxically overexpressed in CRC and as such may play an unappreciated role in tumorigenesis. The exact mechanism of GADD45B inactivation and overexpression requires further investigation. GADD45B could be a potential therapeutic target for CRC treatment in future.

Gadd45 in Stress Signaling, Cell Cycle Control, and Apoptosis

“…In one study, point mutations were found in exon four of the Gadd45a gene in 14 % of pancreatic cancer samples, and Gadd45a expression in p53-positive tumors was associated with a lower patient survival rate. Gadd45b expression was associated with increased relapse and patient death in human colorectal carcinoma (Wang et al 2012 ) Gadd45a induction also protects melanoma cells from UV radiation-induced death. Lack of Gadd45a induction in cervical carcinomas correlates with a good clinical response to radiotherapy (Gao et al 2009 ).…”

Enriched variations in TEKT4 and breast cancer resistance to paclitaxel

“…A granular cytoplasmic stain was defined as positive. Briefly, the staining index (SI, range 0-9) was calculated as the result of the intensity score (0, no staining; 1 þ , faint/equivocal; 2 þ , moderate; 3 þ , strong) and the distribution score (0, no staining; 1 þ , staining of o10% of cells; 2 þ , between 10 and 50% of cells; and 3 þ , staining of 450% of cells) 52 . For tektin4 protein in this study, a moderate/strong cytoplasmic staining (SI ¼ 5-9) was defined as tektin4-high, while a weak or negative staining (SI ¼ 0-4) was defined as tektin4-low/normal 53,54 .…”

Long‐term soy consumption and tumor tissue MicroRNA and gene expression in triple‐negative breast cancer

“…Functional enrichment analysis using IPA for the downregulated genes revealed that the 2 most significantly enriched pathways were hereditary breast cancer signaling ( P < 1.08 × 10 –4 ) and interleukin 2 signaling ( P < 6.84 × 10 –4 ), both of which were driven by oncogenes KRAS , IL‐2RB , and GADD45B (Fig. D) . For upregulated genes, the most significantly enriched pathway was nucleotide excision repair ( P < 1.54 × 10 –2 ), which was driven by the tumor suppressor gene ERCC1 (Fig.…”

“…1D). 28 For upregulated genes, the most significantly enriched pathway was nucleotide excision repair (P < 1.54 3 10 -2 ), which was driven by the tumor suppressor gene ERCC1 (Fig. 1D).…”