論文 - 詳細
| RRC ID | 77188 |
|---|---|
| 著者 | Kitagawa H, Hiraki M, Namba T, Baba K, Miyake S, Ito K, Tanaka T, Noshiro H. |
| タイトル | The Oncological Effect of Mutant p53 on the Metastatic Phenotype of Gastric Cancer Cells. |
| ジャーナル | Anticancer Res |
| Abstract |
BACKGROUND/AIM:P53 is the most frequently mutated tumor suppressor gene among all cancers. In human cancers, specific residues of p53 are mutated at a high frequency, and those mutations are known as hotspot mutations. Mutant p53 promotes tumor progression through the gain-of-function (GOF) mechanism. However, its biological characteristics, especially its metastatic potential, owing to different hotspot mutations in gastric cancer remain unclear. In the present study, we investigated the p53-depended metastatic phenotype. MATERIALS AND METHODS:This study examined the differences in the metastatic potential of wild-type, mutant-p53-R175H, and mutant-p53-R273H NUGC-4 gastric cancer cells in vitro and in vivo. RESULTS:NUGC-4-mutant-p53-R175H cells showed significant cell proliferation, healing and invasive abilities in proliferation, wound healing and invasion assay, respectively, compared to wild-type and mutant-p53-R273H cells. Both NUGC-4-mutant-p53 cell types expressed epithelial-mesenchymal transition (EMT)-related proteins. Furthermore, NUGC-4-mutant-p53-R175H cells showed less attachment to the extracellular matrix and greater expression of EMT-related proteins than NUGC-4-mutant-p53-R273H cells. Regarding the peritoneal dissemination model, NUCG-4-mutant-p53-R175H and NUCG-4-mutant-p53-R273H cells demonstrated less frequent formation of dissemination nodules than NUGC-4-empty cells. In contrast, liver metastases were more frequent and greater in number in NUCG3-mutant-p53-R175H than in the other cell lines. CONCLUSION:Our results suggest that differences in the p53 status, even in the hotspot mutation site, affect not only the characteristics of the cells but also the metastatic ability of gastric cancer. |
| 巻・号 | 43(11) |
| ページ | 4887-4895 |
| 公開日 | 2023-11-1 |
| DOI | 10.21873/anticanres.16686 |
| PII | 43/11/4887 |
| PMID | 37909947 |
| MeSH | Humans Medical Oncology Phenotype Stomach Neoplasms* / genetics Tumor Suppressor Protein p53 / genetics |
| IF | 1.994 |
| リソース情報 | |
| ヒト・動物細胞 | NUGC-4(RCB1939) |