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

1.转录因子SOX 2上调胃特异性胃蛋白酶原A基因表达SOX 2在正常胃粘膜中表达，但在正常结肠中不表达。为了阐明SOX 2的作用，我们分析了10个胃癌（GC）和10个结直肠癌（CRC）细胞系中SOX 2和胃蛋白酶原（胃的分化标志物）的表达。RT-PCR结果显示，6个胃癌细胞系和5个结直肠癌细胞系均有SOX 2表达。在8个GC和7个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GC和CRC细胞系中，SOX 2的过表达上调内源性胃蛋白酶原A的表达，但不上调胃蛋白酶原C的表达。此外，胃蛋白酶原A的表达显着降低，在GC细胞系中的SOX 2 RNA干扰。结论：1. SOX 2在胃蛋白酶原A的调节中起重要作用，SOX 2的异位表达可能与大肠癌细胞的异常分化有关. Hath 1上调胃 ...更多信息 胃细胞中粘蛋白基因的表达Notch信号通路已知介导细胞分化。我们研究了7个Notch相关基因的mRNA表达，并将其与胃粘蛋白基因MUC 5AC和MUC 6的表达进行比较，在8个胃癌（GC）细胞系中。Notch 1/2/3和Hes 1在大多数胃癌细胞系和正常胃粘膜中表达，而Hes 2/3在这些细胞系和正常胃中均不表达。至于Hath 1，5 GC细胞株表现出检测不到的水平，而正常胃粘膜表达Hath 1。Hath 1和MUC 6在大多数胃癌细胞系中的表达模式密切相关。许多MUC 5AC阳性病例也倾向于显示Hath 1表达。在GC细胞中Math 1的过表达增强MUC 6和MUC 5AC mRNA水平。通过RNA干扰敲低Hath 1显著降低了两种粘蛋白基因的表达。这些数据表明Hath 1是GC细胞中MUC 6和MUC 5AC的转录调节因子之一。Hath 1表达的缺失也可能在胃癌发生中起作用。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