論文 - 詳細
| RRC ID | 59759 |
|---|---|
| 著者 | Ooizumi Y, Kojima K, Igarashi K, Tanaka Y, Harada H, Yokota K, Kaida T, Ishii S, Tanaka T, Yokoi K, Nishizawa N, Washio M, Ushiku H, Katoh H, Kosaka Y, Mieno H, Hosoda K, Watanabe M, Katada C, Hiki N, Yamashita K. |
| タイトル | Comprehensive Exploration to Identify Predictive DNA Markers of ΔNp63/SOX2 in Drug Resistance in Human Esophageal Squamous Cell Carcinoma. |
| ジャーナル | Ann Surg Oncol |
| Abstract |
BACKGROUND:OBP-801 is a novel histone deacetylase inhibitor being developed as an anticancer drug. In this study, we explored genes to predict drug resistance in human cancer. METHODS:OBP-801 resistance was assessed in 37 strains of human cancer cell lines. Expression microarrays harboring 54,675 genes were used to focus on candidate genes, which were validated for both functional and clinical relevance in esophageal squamous cell carcinoma (ESCC). RESULTS:OBP-801 is sensitive to esophageal, gastric, and thyroid cancer, and resistant to some esophageal and colorectal cancers. We therefore used ESCC to explore genes. Comprehensive exploration focused on ΔNp63/SOX2, which were both genetically and epigenetically overexpressed in ESCC. Genomic amplifications of ΔNp63/SOX2 were tightly correlated each other (r = 0.81). Importantly, genomic amplification of ΔNp63/SOX2 in the resected tumors after neoadjuvant chemotherapy was significantly associated with histological grade of response (G1). Forced expression of either of these two genes did not induce each other, suggesting that their functional relevances were independent and showed robust drug resistance in OBP-801, as well as 5-fluorouracil. Furthermore, ΔNp63 could exert a potent oncogenic potential. RNA interference of ΔNp63 supported its oncological properties, as well as drug resistance. CONCLUSION:Comprehensive exploration of genes involved in anticancer drug residence could identify critical oncogenes of ΔNp63/SOX2 that would predict chemotherapy response in ESCC. |
| 巻・号 | 26(13) |
| ページ | 4814-4825 |
| 公開日 | 2019-12-1 |
| DOI | 10.1245/s10434-019-07795-w |
| PII | 10.1245/s10434-019-07795-w |
| PMID | 31529309 |
| MeSH | Aged Antineoplastic Agents / pharmacology Apoptosis Biomarkers, Tumor / genetics* Cell Proliferation Drug Resistance, Neoplasm / genetics* Esophageal Neoplasms / drug therapy Esophageal Neoplasms / genetics* Esophageal Neoplasms / pathology Esophageal Squamous Cell Carcinoma / drug therapy Esophageal Squamous Cell Carcinoma / genetics* Esophageal Squamous Cell Carcinoma / pathology Female Follow-Up Studies Gene Amplification Gene Expression Regulation, Neoplastic Genetic Markers* Humans Male Peptides, Cyclic / pharmacology Prognosis SOXB1 Transcription Factors / genetics* Survival Rate Transcription Factors / genetics* Tumor Cells, Cultured Tumor Suppressor Proteins / genetics* |
| IF | 3.681 |
| 引用数 | 0 |
| リソース情報 | |
| ヒト・動物細胞 | 8305C(RCB1909) |