Abnormal expression of GADD45B in human colorectal carcinoma View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2012-10-30

AUTHORS

Lisha Wang, Xiuying Xiao, Dali Li, Yayun Chi, Ping Wei, Yiqin Wang, Shujuan Ni, Cong Tan, Xiaoyan Zhou, Xiang Du

ABSTRACT

BACKGROUND: GADD45B 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. METHODS: The 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. RESULTS: The 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. CONCLUSION: GADD45B, 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. More... »

PAGES

215-215

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/1479-5876-10-215

DOI

http://dx.doi.org/10.1186/1479-5876-10-215

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1008709195

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/23110778


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43 Gadd45b expression
44 Gadd45b overexpression
45 Kaplan-Meier survival curves
46 PCR
47 TNM stage
48 Western blotting
49 abnormal expression
50 adjacent noncancerous tissues
51 aim
52 analysis
53 apoptosis
54 apoptotic changes
55 apoptotic pathway
56 area
57 arrest DNA damage-inducible gene family
58 blotting
59 carcinoma
60 cell growth control
61 cell lines
62 changes
63 colorectal carcinoma
64 colorectal tissues
65 control
66 curves
67 cytometry
68 damage repair response
69 damage-inducible gene family
70 date
71 death
72 depth
73 disease-free survival
74 exact mechanism
75 expression
76 expression plasmid
77 factors
78 family
79 further investigation
80 future
81 gene family
82 genes
83 growth arrest DNA damage-inducible gene family
84 growth control
85 hand
86 human colorectal carcinoma
87 immunohistochemistry
88 inactivation
89 investigation
90 levels
91 lines
92 mRNA
93 mechanism
94 members
95 multivariate analysis
96 noncancerous tissues
97 normal colorectal tissues
98 overexpression
99 p53-mediated apoptotic pathway
100 pathway
101 patient survival
102 patients
103 plasmid
104 potential therapeutic target
105 protein levels
106 quantitative PCR
107 real-time quantitative PCR
108 relapse
109 repair response
110 response
111 role
112 role of Gadd45b
113 siRNA
114 significant factor
115 stage
116 study
117 suppressor gene
118 survival
119 survival curves
120 target
121 therapeutic target
122 tissue
123 treatment
124 tumor suppressor gene
125 tumorigenesis
126 unappreciated role
127 vitro
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