TIMP-3 and Phosphatidylinositol 3-kinase genes were found to be related to the progression of colon cancer in a comparison of pneumoperitoneum and laparotomy in a murine model.
OBJECTIVE
Laparoscopic surgery has been performed on a wide variety of patients because the clinical benefits of a perioperative recovery result in a better short-time outcome than an open colectomy. However, no basic and molecular-biological examinations have yet to elucidate the mechanisms of such an improved outcome.


METHODS
To examine the gene expression profiles of mice inoculated with colon cancer cells, the tumors, the livers and the lungs of mice were analyzed using a microarray.


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 that 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 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. We observed the expression level of the Skp-2 to be upregulated, while the expression level of p27 protein decreased.


CONCLUSIONS
The surgical procedures of a laparotomy induced a downregulation of TIMP-3 and an upregulation of PI3-kinase, which together resulted in an enhancement of cancer cell growth thus leading to an increased invasion activity and cell cycle in comparison to treatment using a laparoscopic approach.
Tanaka
Fumiaki
F
Division of Molecular and Surgical Oncology, Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 4546 Tsurumihara, Beppu 874-0838, Japan.
Sonoda
Hideto
H
Okamoto
Masahiro
M
Mimori
Koshi
K
Utsunomiya
Tohru
T
Inoue
Hiroshi
H
Hanai
Taizo
T
Mori
Masaki
M
D000818:Animals; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics* / Q000601:surgery; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D010535:Laparoscopy; D007813:Laparotomy; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D020411:Oligonucleotide Array Sequence Analysis; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D011028:Pneumoperitoneum, Artificial; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000235:genetics*
D019717:Tissue Inhibitor of Metalloproteinase-3; D019869:Phosphatidylinositol 3-Kinases