Sox2 expression in human stomach adenocarcinomas with gastric and gastric-and-intestinal-mixed phenotypes.
OBJECTIVE
Other than ectopic expression of intestinal transcription factors, Cdx1 and Cdx2, the molecular mechanisms underlying gastric and intestinal phenotypes of human stomach adenocarcinomas have yet to be clarified in detail. We have reported that Sox2, an HMG-box gastric transcription factor, is expressed in normal gastric mucosa and down-regulated in intestinal metaplasia.


RESULTS
We analysed mRNA levels of Sox2 and other differentiation markers in 50 surgically resected stomach adenocarcinomas, immunohistochemically classified into gastric (G), gastric-and-intestinal (GI)-mixed, solely intestinal (I), and null (N) types. Sox2 was found to be transcribed in G and GI-mixed type adenocarcinomas in accordance with MUC5AC and MUC6 expression, while Cdx1 and Cdx2 were up-regulated in GI-mixed and I types along with the expression of MUC2 and villin. In the N type, both gastric and intestinal transcription factors were suppressed. Immunohistochemistry confirmed expression of Sox2 in MUC5AC+ lesions and Cdx2 localization together with MUC2. A stomach adenocarcinoma cell line, KATOIII, demonstrated both MUC5AC and Sox2, although MUC5AC mRNA was not detected in the Sox2+ AGS cell line.


CONCLUSIONS
Sox2 may play an important role in maintaining a gastric phenotype in stomach cancers as well as in normal tissue, in cooperation with other cofactor(s).
Tsukamoto
T
T
Division of Oncological Pathology, Aichi Cancer Centre Research Institute, Nagoya, Japan. ttsukamt@aichi-cc.jp
Mizoshita
T
T
Mihara
M
M
Tanaka
H
H
Takenaka
Y
Y
Yamamura
Y
Y
Nakamura
S
S
Ushijima
T
T
Tatematsu
M
M
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000071616:CDX2 Transcription Factor; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D024002:HMGB Proteins / Q000032:analysis / Q000235:genetics*; D018398:Homeodomain Proteins / Q000032:analysis / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D007414:Intestinal Neoplasms / Q000378:metabolism / Q000473:pathology*; D008840:Microfilament Proteins / Q000032:analysis / Q000235:genetics; D055271:Mucin 5AC; D055272:Mucin-6; D009077:Mucins / Q000032:analysis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055748:SOXB1 Transcription Factors; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics*
D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D024002:HMGB Proteins; D018398:Homeodomain Proteins; C524678:MUC5AC protein, human; C524734:MUC6 protein, human; D008840:Microfilament Proteins; D055271:Mucin 5AC; D055272:Mucin-6; D009077:Mucins; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D014157:Transcription Factors; C026615:villin