2005 Fiscal Year Final Research Report Summary
Inflammation-caused abnormalities in gastric differentiation and molecular epidemiologic analysis of gastric cancer
| Project/Area Number |
16390168
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hygiene
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
YUASA Yasuhito Tokyo Medical and Dental University, Department of Molecular Oncology, Professor, 大学院・医歯学総合研究科, 教授 (80111558)
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| Co-Investigator(Kenkyū-buntansha) |
AKIYAMA Yoshimitsu Tokyo Medical and Dental University, Department of Molecular Oncology, lecturer, 大学院・医歯学総合研究科, 講師 (80262187)
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| Project Period (FY) |
2004 – 2005
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| Keywords | differentiation / gastric cancer / SOX2 / Mucin / Notch / Hath-1 / MUC6 / apoptosis |
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| Research Abstract |
1. Transcription factor SOX2 up-regulates stomach- specific pepsinogen A gene expression
SOX2 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 cells
The 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
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