論文 - 詳細
| RRC ID | 1376 |
|---|---|
| 著者 | Ikenoue T, Hikiba Y, Kanai F, Aragaki J, Tanaka Y, Imamura J, Imamura T, Ohta M, Ijichi H, Tateishi K, Kawakami T, Matsumura M, Kawabe T, Omata M. |
| タイトル | Different effects of point mutations within the B-Raf glycine-rich loop in colorectal tumors on mitogen-activated protein/extracellular signal-regulated kinase kinase/extracellular signal-regulated kinase and nuclear factor kappaB pathway and cellular transformation. |
| ジャーナル | Cancer Res |
| Abstract |
Recently, mutations in the B-Raf gene have been identified in a variety of human cancers, such as melanoma and colorectal carcinoma, and more than 80% of the B-Raf mutations have been V599E. Although other mutations have been reported, their functional consequences are poorly understood. In our earlier study, we demonstrated that colon tumor-associated B-Raf mutations within the kinase activation segment are not necessarily associated with an increase in mitogen-activated protein/extracellular signal-regulated kinase kinase/extracellular signal-regulated kinase (MEK/Erk) or nuclear factor kappaB (NFkappaB) signaling activity or in NIH3T3-transforming ability. In this study, we examined the effect of colon tumor-associated mutations within the B-Raf glycine-rich loop (G loop) on MEK/Erk and NFkappaB signaling and on the transformation of NIH3T3 fibroblasts or IEC-6 intestinal epithelial cells. Of the six G loop mutations examined, only the B-Raf G468A significantly increased MEK/Erk and NFkappaB signaling and NIH3T3 transformation. Only this mutation induced transformed phenotypes of IEC-6 cells. In contrast, the B-Raf G468E mutation significantly decreased MEK/Erk signaling and NIH3T3 transformation and had no effect on NFkappaB signaling. The B-Raf F467C mutation moderately elevated MEK/Erk signaling and NIH3T3 transformation. The other three B-Raf mutations, R461I, I462S, and G463E, did not increase MEK/Erk or NFkappaB signaling or NIH3T3 transformation. Except for F467C, none of the tumors with B-Raf mutations examined in this study had K-Ras mutations. These results suggest that some of the B-Raf G loop mutations reported in colorectal tumors do not increase kinase or transforming activities but might contribute to carcinogenesis via other mechanisms or be irrelevant to carcinogenesis. |
| 巻・号 | 64(10) |
| ページ | 3428-35 |
| 公開日 | 2004-5-15 |
| DOI | 10.1158/0008-5472.CAN-03-3591 |
| PII | 64/10/3428 |
| PMID | 15150094 |
| MeSH | Amino Acid Sequence Animals COS Cells Cell Adhesion / genetics Cell Division / genetics Cell Transformation, Neoplastic / genetics* Cell Transformation, Neoplastic / metabolism Chlorocebus aethiops Colorectal Neoplasms / enzymology Colorectal Neoplasms / genetics* Enzyme Activation Humans I-kappa B Kinase MAP Kinase Signaling System / genetics* Mice Mitogen-Activated Protein Kinases / genetics Mitogen-Activated Protein Kinases / metabolism* Molecular Sequence Data NF-kappa B / metabolism* NIH 3T3 Cells Point Mutation* Protein Serine-Threonine Kinases / metabolism Proto-Oncogene Proteins B-raf Proto-Oncogene Proteins c-raf / genetics* Proto-Oncogene Proteins c-raf / metabolism Sequence Alignment Signal Transduction Transcription, Genetic |
| IF | 9.727 |
| 引用数 | 55 |
| WOS 分野 | ONCOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | IEC 6(RCB0993) |