Down-regulation of Gadd45 expression is associated with tumor differentiation in non-small cell lung cancer.
BACKGROUND
Evidence suggests that the growth arrest and DNA damage-inducible gene 45 (Gadd45) is an effective indicator of poor prognosis or malignant potential in solid tumors. The purpose of this study was to determine the gene expression patterns and clinical relevance of Gadd45 in tumor specimens of non-small cell lung cancer (NSCLC) patients.


METHODS
Using a quantitative real-time RT-PCR method, the mRNA expression of Gadd45 was analyzed in tumor and paired normal-appearing tissues of 66 patients with NSCLC. The gene expression data for each patient were matched to the clinicopathological parameters.


RESULTS
Gadd45 mRNA expression was detectable in all (100%) specimens analyzed. The overall median mRNA expression level of Gadd45 was approximately 10-fold lower in tumor tissues than in matching normal lung tissues (p < 0.001). High intratumoral Gadd45 expression was significantly associated with a poorer histological grading (p = 0.041).


CONCLUSIONS
The significant decrease in Gadd45 expression in tumors compared with normal tissue and its association with histological grading suggest a role for Gadd45 in the differentiation pathway of NSCLC.
Higashi
Hiroshi
H
Department of Visceral and Vascular Surgery, University of Cologne, Cologne, Germany.
Vallböhmer
Daniel
D
Warnecke-Eberz
Ute
U
Hokita
Shuichi
S
Xi
Huan
H
Brabender
Jan
J
Metzger
Ralf
R
Baldus
Stephan E
SE
Natsugoe
Shoji
S
Aikou
Takashi
T
Hölscher
Arnulf H
AH
Schneider
Paul M
PM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D018797:Cell Cycle Proteins / Q000096:biosynthesis* / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D000097642:GADD45 Proteins
D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; C439070:GADD45A protein, human; D000097642:GADD45 Proteins