2005 Fiscal Year Final Research Report Summary
Peroxisome proliferator activated receptor gamma gene in colorectal cancer containing wild-type K-ras gene
| Project/Area Number |
16590292
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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 |
Human pathology
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| Research Institution | Dokkyo Medical University |
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Principal Investigator |
TOMITA Shigeki Dokkyo Medical University, Surgical and Molecular Pathology, Assistant Professor, 医学部, 講師 (90275751)
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| Co-Investigator(Kenkyū-buntansha) |
ONO Yuko Dokkyo Medical University, Surgical and Molecular Pathology, Associate Professor, 医学部, 助教授 (90254961)
OHKURA Yasuo Dokkyo Medical University, Surgical and Molecular Pathology, Associate Professor, 医学部, 助教授 (30312284)
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| Project Period (FY) |
2004 – 2005
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| Keywords | Colorectal cancer / K-ras / pparγ / Progression |
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| Research Abstract |
Several studies suggest that approximately 50% of colorectal cancer contains activated-point mutation in K-ras gene at chodon 12. The muation occurs in early stage during adenoma-carcinoma sequence in colon cancer development. However, remaing 50% of colorectal cancer, which developed in adenoma-carcinoma sequencem contains wild-type K-ras gene.
On the other hand, epidemiological data suggests that patients with diabetes mellitus have a high risk for colorectal cancer. However, no explanation based on the molecular analysis has been shown for their association.
Peroxisome proliferator activated receptor gamma (pparγ) is a family of transcription factors and a member of nuclear hormone receptor superfamily. Furthermore, pparγ is reported to be a candidate for tumor suppressor gene. Ppar γ inhibits the growth of several types of cells and induces the differentiation and apoptosis.
It is also know that, pparγ participates in developmental process for type 2 diabetes mellitus. Recent studies
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have suggested that a Pro12Ala polymorphism of pparγ gene affects the receptor activity. Furthermore, there is cross talk between the RAS/MAPK signal transduction pathway and pparγ signal transduction pathway. We have previously shown that pparγ gene polymorphism (Pro/Ala, Ala/Ala) may be implicated with development of colorectal cancers, in which K-ras gene is not mutated.
Cyclooxynase-2 (COX-2) and cyclin D1 protein expression are up-regulated in colorectal cancer tissue. COX-2 and cyclin D1 are target protein which in RAS/MAPK signal transduction and pparγ signal transduction pathway. But no report based on these genes analyses has been shown for their expression pattern.
In this investigation, we analyzed these transduction pathway target protein (COX-2, cyclin D1) and the pparγ gene polymorphism. K-ras gene status in colorectal cancer.
We found abnormal expression pattern of COX-2 and cyclin D1 independent status of these genes. But in this study down-regulated pparγ gene polymorphism was found only in one patient in which K-ras gene is not mutated.
Then we are going to study expression pattern of COX-2 and cyclin D1 in a lot of patient with colorectal cancer and examined the association of two genetic alterations in development of colorectal cancer. Less
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