2004 Fiscal Year Final Research Report Summary
Phosphatidylinositol 3-kinase and TIMP-3 genes were found to be related to the progression of colon cancer during laparoscopic surgery in a murine model.
| Project/Area Number |
15591411
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
UTSUNOMIYA Tohru Kyushu University, Kyushu Univ.Hospital, Assistant Professor, 大学病院, 講師 (30304801)
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| Co-Investigator(Kenkyū-buntansha) |
TANAKA Fumiaki Kyushu University, Kyushu Univ.Hospital, Research Associate, 大学病院, 助手 (30332836)
MORI Masaki Kyushu University, Medical Institute of Bioregulation, Professor, 生体防御医学研究所, 教授 (70190999)
YOSHITAKE Shinichirou Kyushu University, Kyushu Univ.Hospital, Research Associate, 大学病院, 助手 (80315142)
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| Project Period (FY) |
2003 – 2004
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| Keywords | Laparoscopic suergery / Colorectal cancer / Cytokines / DNA microarray / Gene expression / Mouse |
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| Research Abstract |
Objective : The aim of this study was to determine the gene expression patterns of laparoscopic procedures to identify any benefits in comparison with laparotomy procedures.
Summary and background data : Laparosopic surgery has been performed on a wide variety of patients because of the clinical benefits of perioperative recovery, result in a better survival than an open colectomy. However, no basic and molecular-biological examinations have yet to elucidate the mechanisms of such an increased survival.
Methods : To examine the gene expression profiles of mice innoculated with colon cancer cells, the tumors, the livers and the lungs of mice were analyzed using a microarray after either laparoscopic treatment, an open laparotomy or anesthesia alone.
Results : In the laparotomy and control group, we observed a significant enhancement of tumor growth in comparison to the laparoscopic group. When analyzing the genes became more remarkably upregulated or downregulated in the laparoscopic group in comparison to those in the laparotomy or control group, we focused our attention on the TIMP-3 gene and PI3-kinase gene expression. The downregulation of TIMP-3,which played an important role in enhancing invasion the activity of the tumor cells, and the upregulation of PI3-kinase were observed. To confirm the downstream signal of the PI3-kinase gene, we examined the expression of Skp-2 gene and p27 protein, which were key molecules for regulating the cell cycle. We observed that the expression level of the Skp-2 to be upregulated, while the expression level of p27 protein decreased.
Conclusion : These results suggest that the surgical procedures of a laparotomy induced a dwonregulation of TIMP-3 and an upregulation of PI3-kinase, which together resulted in an enhancement of cancer cell growth leading to an increased invasion activity and cell cycle in comparison to treatment using a laparoscopic approach.
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