title: Abnormal expression of GADD45B in human colorectal carcinoma.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.
authors.forename: Lisha
authors.initials: L
authors.lastname: Wang
authors.forename: Xiuying
authors.initials: X
authors.lastname: Xiao
authors.forename: Dali
authors.initials: D
authors.lastname: Li
authors.forename: Yayun
authors.initials: Y
authors.lastname: Chi
authors.forename: Ping
authors.initials: P
authors.lastname: Wei
authors.forename: Yiqin
authors.initials: Y
authors.lastname: Wang
authors.forename: Shujuan
authors.initials: S
authors.lastname: Ni
authors.forename: Cong
authors.initials: C
authors.lastname: Tan
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhou
authors.forename: Xiang
authors.initials: X
authors.lastname: Du
mesh_terms: D000368:Aged; D000943:Antigens, Differentiation / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D015153:Blotting, Western; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000378:metabolism*; D017931:DNA Primers; D018572:Disease-Free Survival; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D000097642:GADD45 Proteins
chemical_list: D000943:Antigens, Differentiation; D017931:DNA Primers; D012333:RNA, Messenger; C086470:GADD45B protein, human; D000097642:GADD45 Proteins