2007 Fiscal Year Final Research Report Summary
Strong HLA-DR antigen expression on cancer cells relates to better prognosis of colorectal cancer patients : Possible involvement of c-myc suppression by IFN-γ in situ
| Project/Area Number |
18591454
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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 | Chiba University |
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Principal Investigator |
NISHIMORI Takanori Chiba University, HOSPITAL, FRONTIER SURGERY, ASSISTANT PROFESSOR (30401003)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUSHITA Kazuyuki CHIBA UNIVERSITY, HOSPITAL, EMERGENCY AND CRITICAL CARE MEDICINE, ASSISTANT PROFESSOR (90344994)
TOMONAGA Takeshi CHIBA UNIVERSITY, GRADUATE SCHOOL OF MEDICIE, MOLECULAR DIAGNOSIS, ASSOCIATE PROFESSOR (80227644)
NOMURA Fumio CHIBA UNIVERSITY, GRADUATE SCHOOL OF MEDICIE, MOLECULAR DIAGNOSIS, PROFESSOR (80164739)
SHIMADA Hideaki CHIBA UNIVERSITY, GRADUATE SCHOOL OF MEDICIE, FRONTIER SURGERY, ASSOCIATE PROFESSOR (20292691)
SUNAGA Masahiko CHIBA UNIVERSITY, HOSPITAL, MOLECULAR DIAGNOSIS, ASSISTANT PROFESSOR (10361437)
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| Project Period (FY) |
2006 – 2007
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| Keywords | Human Leukocyte Antigen / HLA-DR antigen / cytokine / c-myc gene / helper T-cell |
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| Research Abstract |
Strong HLA-DR antigen expression on cancer cells relates to better prognosis of colorectal cancer patients, although the precise mechanism is controversial. From an immunologic point of view, HLA-DR antigen, induced by IFN-γ, is required for tumor-associated antigen recognition by CD4+ T cells. For instance, as reported previously, the expression of HLA-DR antigen in normal colorectal epithelium immediately adjacent to cancer coincided significantly with the existence of IFN-γ mRNA in the tissue. From another aspect, IFN-γ has been revealed to suppress c-myc expression in vivo through stat1-dependent mechanism, which is important for cell growth, cell cycle, and chromosome instability. In this study, strong HLA-DR-positive expression on cancer cells, as expectedly, was significantly related to better prognosis of colorectal cancer patients. High IFN-γ mRNA expression in situ indicated significantly less activation of c-myc mRNA expression. Further, HLA-DR antigen expression in cancer cells, as well as Dukes stages, was an independent factor for better long-term survival by multivariate analysis. Taken together, IFN-γ, which induces HLA-DR antigens on the cell surface, also suppresses c-myc expression in situ, and is a possible non-immunologic mechanism involved in the better long-term survival of colorectal cancer patients.
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