| RRC ID |
42485
|
| 著者 |
Okuda H, Toyota M, Ishida W, Furihata M, Tsuchiya M, Kamada M, Tokino T, Shuin T.
|
| タイトル |
Epigenetic inactivation of the candidate tumor suppressor gene HOXB13 in human renal cell carcinoma.
|
| ジャーナル |
Oncogene
|
| Abstract |
Epigenetic alterations like DNA methylation and the resulting inactivation of cancer-related genes often contribute to the development of various cancers. To identify the genes that are silenced by aberrant methylation in renal cell carcinoma (RCC), we subjected two RCC lines to methylated CpG island amplification/representational difference analysis. This identified 27 CpG islands. Combined bisulfite restriction analysis of these CpG islands in primary RCC cases revealed that four were methylated in a tumor-specific manner. One of these was identified as the human homeo-box gene B13 (HOXB13) gene, but the remaining three CpG islands were not associated with known genes. The methylation frequencies of HOXB13 in primary RCC samples and lines were 30 and 73%, respectively. The methylation status of HOXB13 correlated with the loss of its expression both in RCC lines and primary tumors, and methyltransferase inhibitor treatment induced the recovery of its expression. Exogenous expression of HOXB13 in RCC cells that lacked endogenous HOXB13 expression suppressed colony formation and induced apoptotic features. Furthermore, HOXB13 methylation correlated positively with tumor grade and microvessel invasion. These results suggest that HOXB13 is a novel candidate tumor suppressor gene in RCC and that its inactivation may play an important role in both RCC tumorigenesis and progression.
|
| 巻・号 |
25(12)
|
| ページ |
1733-42
|
| 公開日 |
2006-3-16
|
| DOI |
10.1038/sj.onc.1209200
|
| PII |
1209200
|
| PMID |
16278676
|
| MeSH |
Apoptosis / physiology
Carcinoma, Renal Cell / genetics*
Cell Line, Tumor
CpG Islands
DNA Methylation
Epigenesis, Genetic*
Gene Silencing
Genes, Tumor Suppressor*
Homeodomain Proteins / genetics*
Homeodomain Proteins / metabolism
Humans
Immunohistochemistry
Kidney Neoplasms / genetics*
Reverse Transcriptase Polymerase Chain Reaction
|
| IF |
7.971
|
| 引用数 |
59
|
|
WOS 分野
|
GENETICS & HEREDITY
ONCOLOGY
BIOCHEMISTRY & MOLECULAR BIOLOGY
CELL BIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
TUHR4TKB(RCB1198)
TUHR14TKB(RCB1383) |
