2000 Fiscal Year Final Research Report Summary
Mechanism of abnormality in p27^<K1P1> expression in human lung cancer and its therapeutic application
| Project/Area Number |
11670159
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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 |
Pathological medical chemistry
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| Research Institution | Aichi Cancer Center Research Institute |
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Principal Investigator |
MASUDA Akira Aichi Cancer Center Research Institute, Division of Molecular Oncology, Senior Researcher, 分子腫瘍学部, 主任研究員 (50157202)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Takashi Aichi Cancer Center Research Institute, Division of Molecular Oncology, Research Head, 分子腫瘍学部, 部長 (50231395)
HIDA Toyoaki Aichi Cancer Center Research Institute, Research Institute, Researcher, 研究所, 研究員 (80250249)
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| Project Period (FY) |
1999 – 2000
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| Keywords | Lung Cancer / p27^<K1P1> / Small Cell Lung Cancer / Cell Cycle / Apoptosis |
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| Research Abstract |
A previous study of ours unexpectedly found that in contrast to frequent reduction in non-small cell lung cancer (NSCLC) in association with poor prognosis, high expression of the p27^<K1P1> cyclin-dependent kinase (CDK) inhibitor was retained in virtually all small cell lung cancers (SCLCs), which represent the most aggressive form of lung cancer. This observation suggested the possibility that highly expressed p27^<K1P1> in SCLC may be non-functional, possibly due to multiple genetic defects in this tumor type. Biochemical analyses, however, revealed that p27^<K1P1> in SCLC is functional aas a CDK inhibitor, clearly showing induction apparently associated with G1/G0 arrest and efficient inhibition of cyclin-CDK kinase activities. Interestingly, we could show that induction of p27^<K1P1> confers on SCLC cells the ability to survive under culture conditions unfavorable for cell growth such as a lack of nutrients and hypoxia. Subsequent transfection experiments with p27^<K1P1> supported this notion. These obsevations suggest that high expression of p27^<K1P1> in vivo may favor the survival of SCLC by preventing apoptosis in a microenvironment unfavorable for cell proliferation.
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