Tani Yasuyo, Akiyama Yoshimitsu, Fukamachi Hiroshi, Yanagihara Kazuyoshi, Yuasa Yasuhito
Department of Molecular Oncology, Graduate School of Medicine and Dentistry, Tokyo Medical and Dental University, 1-5-45, Yushima, Tokyo 113-8519, Japan.
J Cancer Res Clin Oncol. 2007 Apr;133(4):263-9. doi: 10.1007/s00432-006-0165-x. Epub 2006 Nov 28.
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.
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.
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.
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.
转录因子SOX2在正常胃黏膜中表达,但在正常结肠中不表达。我们旨在参照胃蛋白酶原在胃肠道上皮中的表达来阐明SOX2的作用。
我们分析了10种胃癌(GC)和10种结直肠癌(CRC)细胞系中SOX2和胃蛋白酶原(胃的分化标志物)的表达情况。还检测了SOX2过表达和下调对胃蛋白酶原表达的影响。
在RT-PCR检测中,6种GC细胞系和5种CRC细胞系显示有SOX2表达。在8种GC细胞系和7种CRC细胞系中可检测到胃蛋白酶原A的表达,而大多数细胞系表达胃蛋白酶原C。在293T人胚肾细胞以及一些GC和CRC细胞系中,SOX2过表达上调了胃蛋白酶原A的表达,但未上调胃蛋白酶原C的表达。此外,在两种GC细胞系中,SOX2 RNA干扰显著降低了胃蛋白酶原A的表达。
这些数据表明SOX2在胃蛋白酶原A的调控中起重要作用,且SOX2的异位表达可能与结直肠癌细胞的异常分化有关。