Nuclear or cytoplasmic localization of Bag-1 distinctly correlates with pathologic behavior and outcome of gastric carcinomas.
Bag-1 is an antiapoptotic protein with its altered expression and localization in malignancies. To clarify the role of Bag-1 in gastric carcinogenesis, its expression was examined by immunohistochemistry and in situ hybridization on a tissue microarray containing gastric carcinomas, adjacent nonneoplastic mucosa (NNM), adenomas, intestinal metaplasia (IM), or gastritis. Gastric carcinoma tissue and cell lines were studied for Bag-1 expression by Western blot and reverse transcriptase-polymerase chain reaction (RT-PCR). The results demonstrated that Bag-1 proteins were differentially expressed in the nucleus or cytosol of MKN28, AGS, MKN45, KATO-III, or HGC-27 cell lines, despite similar levels of messenger RNA (mRNA) expression. The Bag-1 mRNA overexpression was detectable in 73.3% of 15 gastric carcinomas without significant difference in its encoding products' levels. The nuclear Bag-1 expression gradually decreased from gastritis, IM, adenoma to carcinoma (P < .05), and negatively correlated with lymphatic invasion or lymph node metastasis, cytoplasmic Bag-1 expression, negative parafibromin expression, and poor prognosis (P < .05). Cytoplasmic Bag-1 was weakly immunoreactive in carcinomas, compared with gastritis (P < .05), and positively associated with invasive depth and poor prognosis of the carcinoma (P < .05). The positive rate of Bag-1 mRNA expression was higher in adjacent IMs than carcinomas or adjacent NNM (P < .05). Bag-1 mRNA was expressed more in carcinomas from female patients than the male counterparts (P < .05). There was a positive correlation of Bag-1 mRNA expression with invasive depth and venous invasion (P < .05). Our study indicated that aberrant expression and subcellular distribution of Bag-1 might play an important role in the malignant transformation of gastric epithelial cells and should be considered as a biomarker for gastric carcinogenesis, subsequent progression, and prognosis.
Zheng
Hua-chuan
HC
Department of Biochemistry and Molecular Biology, College of Basic Medicine, China Medical University, Shenyang, 110001 China. zheng_huachuan@hotmail.com
Xu
Xiao-yan
XY
Xing
Ya-nan
YN
Wei
Zheng-li
ZL
Takahashi
Hiroyuki
H
Masuda
Shinji
S
Takano
Yasuo
Y
D000236:Adenoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D014408:Biomarkers, Tumor / Q000378:metabolism; D015153:Blotting, Western; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D005756:Gastritis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008679:Metaplasia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
C091732:BCL2-associated athanogene 1 protein; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D014157:Transcription Factors