| RRC ID |
66095
|
| 著者 |
Egashira S, Jinnin M, Ajino M, Shimozono N, Okamoto S, Tasaki Y, Hirano A, Ide M, Kajihara I, Aoi J, Harada M, Igata T, Masuguchi S, Fukushima S, Ihn H.
|
| タイトル |
Chronic sun exposure-related fusion oncogenes EGFR-PPARGC1A in cutaneous squamous cell carcinoma.
|
| ジャーナル |
Sci Rep
|
| Abstract |
Cutaneous squamous cell carcinoma (cSCC) differs from SCC of other organs in its strong association with chronic sun exposure. However, the specific driver mutations in cSCC remain unknown. Fusion genes in established cSCC cell lines (A431 and DJM-1) were predicted by transcriptome sequence, and validated by Sanger sequence, fluorescence in situ hybridization and G-banding. By transcriptome sequencing, we identified fusion gene EGFR-PPARGC1A in A431, which were expressed in 31 of 102 cSCCs. The lesions harboring the fusion gene tended to be located in sun-exposed areas. In vivo cutaneous implantation of EGFR-PPARGC1A-expressing NIH3T3 induced tumors resembling human cSCC, indicating its potent tumorigenicity. NIH3T3 transfected with EGFR-PPARGC1A as well as A431 showed increased cell proliferation activity. With regard to underlying mechanism, EGFR-PPARGC1A protein causes constitutive tyrosine phosphorylation, and induces the phosphorylation of wild-type full-length epidermal growth factor receptor (EGFR) by dimerization. Conversely, the RNAi-mediated attenuation of EGFR or CRISPR/Cas9-mediated knockdown of the fusion gene in A431 led to a decrease in the cell number, and may have therapeutic value. Our findings advance the knowledge concerning genetic causes of cSCC and the function of EGFR, with potential implications for new diagnostic and therapeutic approaches.
|
| 巻・号 |
7(1)
|
| ページ |
12654
|
| 公開日 |
2017-10-4
|
| DOI |
10.1038/s41598-017-12836-z
|
| PII |
10.1038/s41598-017-12836-z
|
| PMID |
28978917
|
| PMC |
PMC5627299
|
| MeSH |
Animals
CRISPR-Cas Systems
Carcinoma, Squamous Cell / etiology
Carcinoma, Squamous Cell / genetics*
Carcinoma, Squamous Cell / pathology
Cell Line, Tumor
Cell Movement / radiation effects
Cell Proliferation / radiation effects
ErbB Receptors / genetics
Gene Expression Regulation, Neoplastic / radiation effects
Humans
In Situ Hybridization, Fluorescence
Mice
NIH 3T3 Cells
Oncogene Proteins, Fusion / genetics*
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / genetics*
Skin Neoplasms / genetics*
Skin Neoplasms / pathology
Sunlight / adverse effects
Transcriptome / radiation effects
|
| IF |
3.998
|
| リソース情報 |
| ヒト・動物細胞 |
DJM-1(RCB0736) |
