2007 Fiscal Year Final Research Report Summary
Study of hypermethylated and cancer-related genes in the early stage of lung adenocarcinoma.
| Project/Area Number |
17590292
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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 | University of Tsukuba |
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Principal Investigator |
NOGUCHI Masayuki University of Tsukuba, Graduate School of Comprehensive Human Sciences, Professor (00198582)
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| Project Period (FY) |
2005 – 2007
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| Keywords | lung adenocarcinoma / carcinogenesis / methylation / SAMD14 |
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| Research Abstract |
Aberrant methylation of promoter CpG islands is known to be a major inactivation mechanism of tumor suppressor and tumor-related genes. In order to identify novel hypermethylated genes in early-stage lung adenocarcinoma, we performed methylated CpG island amplification (MCA), modified suppression subtractive hybridization (SSH) and methylation-specific PCR (MSP) to identify aberrant methylation of CpG islands in the A/J mouse lung adenoma model, which histologically mimics the early stage of human pulmonary adenocarcinoma. Through MCA, SSH and differential screening (DS), we detected five genes that were hypermethylated in mouse adenoma tissue. Among the five genes, three of them have human homologues, and two of the three showed down-regulation of their expression in human lung adenocarcinoma. Of these two genes, we selected sterile alpha motif domain 14 (SAMD14) and further analyzed its methylation status and expression level by methylation-specific PCR (MSP) and quantitative real time PCR (qRT-PCR). Hypermethylation at the CpG site of the SAMD14 promoter region was detected frequently in early invasive adenocarcinoma (8/24, 33.3%) but not in in situ adenocarcinoma (0/7, 0%) or normal lung tissue (0/31, 0%). Most of the lung adenocarcinoma cell lines examined showed suppressed expression of SAMD14 together with hypermethylation at the promoter region, although an immortalized bronchial epithelium cell line (PL16B) did not show hypermethylation and did express SAMD14. These data suggest that methylation of the SAMD14 gene promoter region is a specific event in pulmonary adenocarcinogenesis and is associated with malignant progression.
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