Transcription factor SOX2 up-regulates stomach-specific pepsinogen A gene expression.
OBJECTIVE
Transcription factor SOX2 is expressed in normal gastric mucosae but not in the normal colon. We aimed to clarify the role of SOX2 with reference to pepsinogen expression in the gastrointestinal epithelium.


METHODS
We analyzed expression of SOX2 and pepsinogens, differentiation markers of the stomach, in ten gastric cancer (GC) and ten colorectal cancer (CRC) cell lines. The effects of over-expression and down-regulation of SOX2 on pepsinogen expression were also examined.


RESULTS
Six GC and five CRC cell lines showed SOX2 expression on RT-PCR. Expression of pepsinogen A was detectable in eight GC and seven CRC cell lines, whereas the majority of the cell lines expressed pepsinogen C. Over-expression of SOX2 up-regulated expression of pepsinogen A but not that of pepsinogen C in 293T human embryonic kidney cells, and some GC and CRC cell lines. Moreover, pepsinogen A expression was significantly reduced by SOX2 RNA interference in two GC cell lines.


CONCLUSIONS
These data suggest that SOX2 plays an important role in regulation of pepsinogen A, and ectopic expression of SOX2 may be associated with abnormal differentiation of colorectal cancer cells.
Tani
Yasuyo
Y
Department of Molecular Oncology, Graduate School of Medicine and Dentistry, Tokyo Medical and Dental University, 1-5-45, Yushima, Tokyo 113-8519, Japan.
Akiyama
Yoshimitsu
Y
Fukamachi
Hiroshi
H
Yanagihara
Kazuyoshi
K
Yuasa
Yasuhito
Y
D000818:Animals; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000503:physiopathology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005753:Gastric Mucosa / Q000201:enzymology / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D024002:HMGB Proteins / Q000378:metabolism*; D006801:Humans; D020116:Pepsinogen A / Q000235:genetics*; D020115:Pepsinogen C / Q000235:genetics; D010957:Plasmids; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000378:metabolism; D055748:SOXB1 Transcription Factors; D013270:Stomach / Q000201:enzymology* / Q000503:physiopathology; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000503:physiopathology; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D004268:DNA-Binding Proteins; D024002:HMGB Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D014157:Transcription Factors; D020115:Pepsinogen C; D020116:Pepsinogen A