Project/Area Number |
07671367
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Digestive surgery
|
Research Institution | University of Tokyo |
Principal Investigator |
SETO Yashuyuki University of Tokyo, Department of Surgery, Assistant, 医学部・附属病院, 助手 (00260498)
|
Co-Investigator(Kenkyū-buntansha) |
KAIZAKI Shoichi University of Tokyo, Department of Sugery, Assistant, 医学部・附属病院, 助手 (70291325)
ISHIMARU Gosei University of Tokyo, Department of Sugery, Assistant, 医学部・附属病院, 助手 (70272557)
TOMINAGA Osamu University of Tokyo, Department of Surgery, Assistant, 医学部・附属病院, 助手 (10261976)
NAGAWA Hirokazu University of Tokyo, Department of Surgery, Assistant Proffesor, 医学部・附属病院, 助教授Eの発現バラン (80228064)
|
Project Period (FY) |
1995 – 1997
|
Project Status |
Completed (Fiscal Year 1997)
|
Budget Amount *help |
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1997: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1996: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1995: ¥1,400,000 (Direct Cost: ¥1,400,000)
|
Keywords | Tumor suppressor gene / Cyclin / Cyclin dependent kinase / Esophageal cancer / Cell cycle / p53 / Rb / p21 / p16 / Cyclin depenaIent Kinase / WAF1 / MTS1 |
Research Abstract |
To study the alterd mechanisms of cell proliferation control in esophageal cancer, expression of the cell cycle regulatous were analyzed in a series of esophageal cancer cell lines and resected specimens of human esophageal cancer. p53, p21^<WAF1/CIP1>, p16^<CDKN2> and Rb were analyzed by Western blotting in 25 esophageal cancer cell lines. p53 and p21^<WAF1/CIP1> were expressed in about 70% of the cell lines, shile p16^<CDKN2> was expressed in a few esophageal cancer cell lines. Rb protein was expressed in all the cell lines studied and phosphorylated and hypophosphorylated forms of Rb were identified. Both p53-dependent and p53-independent pathways appear to be involved in p21 expression. Distinct expression patterns of cell cycle gulatours may reflect different biological characteristics of the cancer cells and different genetic backgrouds to acquire malignant phenotype. To evaluate and compare the levels of cyclin expression, flow cytomertric analysis was performed using human lymphocytes as a conrtrol. Increased expressions of cyclin A,D1, D3 and E were found in 23.1% (6/26), 65.4% (17/26), 15.4% (4/26) and 57.7% (15/26) of the cell lines, respectively. All cell lines studied expressed less cyclin D2 than lymphocytes and the majority of the cell lines expressed cyclin D3 at levels similar to those of lymphocytes. Five cell lines expressed exceptionally high levels of cyclin E.Expressions of cyclin D1 and E were significantly elevated as compared to those of cyclin A,D2 and D3. These results suggest that increased expressions of the positive cell cycle regulatous cyclin D1 and E may play an important role in esophageal carcinogenesis. Even in the limited number of resected specimens of esophageal cancer, similar results were obtained.
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