Identification of new cancer-associated genes at the frequent chromosomal deletion regions of lung cancer
| Project/Area Number |
16590744
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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 |
Respiratory organ internal medicine
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| Research Institution | Aichi Cancer Center Research Institute (2005)
Nagoya University (2004) |
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Principal Investigator |
SEKIDO Yoshitaka Aichi Cancer Center Research Institute, Division of Molecular Oncology, Chief, 部長 (00311712)
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| Co-Investigator(Kenkyū-buntansha) |
SHIMOKATA Kaoru Nagoya University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (10022906)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | Lung cnacer / Chromosomal alteration / Homozygous deletion / Tumor suppressor gene / Gene cloning / Somatic mutation / Carcinogenesis |
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| Research Abstract |
We studied chromosomal 8p11 region that has been shown to be frequently deleted in non-small cell lung cancer (NSCLC). Of 80 surgical specimens studied with D8S1180 marker, we identified 38% tumors with allelic loss. Since SFRP1 is located at 8p11, we tested whether this gene was downregulated in lung cancer and found that 48% of NSCLCs showed low expression. We transfected the SFRP1 expression vector into NSCLC cell lines and found the suppression of colony formation, suggesting that SERP1 is a strong candidate of tumor suppressor gene of lung cancer.
We analyzed the mechanisms of inactivation of 3 tumor suppressor genes (RASSF1A, BLU, and SEMA3B), which are located in the common homozygous deletion region at 3p21.3. Of 138 surgical specimens, we found the promoter hypermethylation in 32% of RASSF1A, 30% in BLU, and 47% of SEMA3B, with the hypermethylation of each gene being detected relatively simultaneously. We analyzed 3pf21.3 allelic loss with D3S1568 and D3S1621 markers using 138 surgical specimens and found that 58% of cases showed allelic loss. We also found that downregulation of SM22 and SPARC, possible downstream genes of RASSF1A, in the RASSF1A-hypermethylated tumors.
We determined that the size of 2p24 homozygous deletion region of NCI-H2882 cell line is about 3.7 MB. Using 128 NSCLC specimens with D2S2150 marker, we found 40% cases with allelic loss. Since RhoB is located in this deletion region, we studied RhoB expression in 20 lung cancer cell lines with Northern blot analysis and 112 surgical specimens with immunohistochemical analysis. We found that frequent downregulation of RhoB, with more frequently downregulated in squamous cell carcinomas than in adenocarcinomas.
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Report
(3 results)
Research Products
(6 results)
