Inflammation-caused abnormalities in gastric differentiation and molecular epidemiologic analysis of gastric cancer

1.转录因子SOX2上调胃特异性胃蛋白酶原A基因的表达SOX2在正常胃粘膜中表达，在正常结肠中不表达。为了阐明SOX2的作用，我们分析了SOX2和胃蛋白酶原在10个胃癌(GC)和10个结直肠癌(CRC)细胞系中的表达。6株胃癌细胞株和5株大肠癌细胞株RT-PCR检测到SOX2的表达。在8个胃癌和7个大肠癌细胞系中检测到胃蛋白酶原A的表达，而大多数细胞系都表达胃蛋白酶原C。SOX2的过度表达上调了内源性胃蛋白酶原A的表达，但不上调胃蛋白酶原C的表达。此外，SOX2 RNA干扰显著降低了胃癌细胞系中胃蛋白酶原A的表达。这些数据提示SOX2在胃蛋白酶原A的调节中起重要作用，SOX2的异位表达可能与结直肠癌细胞的异常分化有关。Hath1上调胃…胃细胞中更多的粘蛋白基因表达Notch信号通路被认为是介导细胞分化的途径。我们研究了7个Notch相关基因在8个胃癌细胞系中的表达，并与胃粘蛋白基因MUC5AC和MUC6的表达进行了比较。NOTCH1/2/3和Hes1在大多数胃癌细胞系和正常胃粘膜中均有表达，而Hes2/3在这些细胞系和正常胃组织中均不表达。至于Hath1，5个GC细胞系未检测到Hath1的表达，而正常胃粘膜表达Hath1。Hath1和MUC6在大多数胃癌细胞系中的表达模式密切相关。许多MUC5AC阳性病例也倾向于Hath1表达。在GC细胞中过表达Math1可增强MUC6和MUC5AC的mRNA水平。RNA干扰抑制Hath1基因后，两种粘蛋白基因的表达均显著降低。这些数据表明，Hath1是GC细胞中MUC6和MUC5AC的转录调控因子之一。Hath1的表达缺失也可能在胃癌的发生中起一定作用。较少

1. Transcription factor SOX2 up-regulates stomach- specific pepsinogen A gene expressionSOX2 is expressed in normal gastric mucosae but not in the normal colon. To clarify the role of SOX2, we analyzed expression of SOX2 and pepsinogens, differentiation markers of the stomach, in 10 gastric cancer (GC) and 10 colorectal cancer (CRC) cell lines. Six GC and five CRC cell lines showed SOX2 expression on RT-PCR. Expression of pepsinogen A was detectable in 8 GC and 7 CRC cell lines, whereas the majority of the cell lines expressed pepsinogen C. Over-expression of SOX2 up-regulated expression of endogenous pepsinogen A but not that of pepsinogen C in GC and CRC cell lines. Moreover, pepsinogen A expression was significantly reduced by SOX2 RNA interference in 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.2. Hath1 up-regulates gastric … More mucin gene expression in gastric cellsThe Notch signaling pathway is known to mediate cell differentiation. We investigated mRNA expression of seven Notch-related genes, and compared it with expression of gastric mucin genes, MUC5AC and MUC6, in 8 gastric cancer (GC) cell lines. Notch1/2/3 and Hes1 were expressed in most GC cell lines as well as normal gastric mucosae, while Hes2/3 were expressed in neither these cell lines nor the normal stomach. As for Hath1, 5 GC cell lines exhibited undetectable levels, while normal gastric mucosa expressed Hath1. The expression patterns of Hath1 and MUC6 were closely related in most GC cell lines. Many MUC5AC-positive cases also tended to show Hath1 expression. Over-expression of Math1 in the GC cells enhanced both the MUC6 and MUC5AC mRNA levels. Knockdown of Hath1 by RNA interference significantly decreased expression of both mucin genes. These data indicate that Hath1 is one of the transcriptional regulators for MUC6 and MUC5AC in GC cells. It is also possible that loss of Hath1 expression may play a role in gastric carcinogenesis. Less