論文 - 詳細
| RRC ID | 38224 |
|---|---|
| 著者 | Yeasmin S, Nakayama K, Rahman MT, Rahman M, Ishikawa M, Iida K, Otsuki Y, Kobayashi H, Nakayama S, Miyazaki K. |
| タイトル | Expression of nuclear Notch3 in cervical squamous cell carcinomas and its association with adverse clinical outcomes. |
| ジャーナル | Gynecol Oncol |
| Abstract |
OBJECTIVE:The aim of this study was to clarify the functional role of Notch3 in human cervical carcinomas. METHODS:Notch3 expression in cervical cancer was assessed by immunohistochemistry, and data on clinical variables were collected by retrospective chart review. We used dual-color fluorescence in situ hybridization (FISH) to analyze DNA copy number alterations in cervical cancer. Inactivation of Notch3 and knocking down Notch3 gene were done using gamma-secretase inhibitor and Notch 3 specific SiRNA to asses Notch3 function in cervical cancer either in vivo or in vitro. RESULTS:Immunohistochemical analysis revealed that Notch3 was significantly overexpressed in cervical squamous cell carcinomas compared with adenocarcinomas. In contrast to normal cervical tissue and cervical intraepithelial neoplasms [CINs], squamous cell carcinomas demonstrated higher nuclear Notch3 immunoreactivity. Notch3 amplification was not found in any cervical carcinomas using FISH analysis. Notch3 nuclear expression was significantly correlated with Jagged-1, a putative Notch3 ligand, and Pbx1b, a potential Notch3 downstream target (P<0.05).Patients with cervical carcinomas positive for nuclear Notch3 expression had significantly shorter overall survival than their peers whose tumors did not express nuclear Notch3. Inactivation of Notch3 decreased cell proliferation and induced apoptosis in ME180 and SKGIIIb cell lines that overexpressed Notch3. Injection of a gamma-secretase inhibitor into ME180 cell tumors established on mice, demonstrated a reduction in tumor growth. CONCLUSION:Our findings suggest that Notch3 might play important role for the proliferation and survival of Notch3 overexpressing tumors and that inactivation of Notch3 may represent a new therapeutic avenue for cervical squamous cell carcinomas. |
| 巻・号 | 117(3) |
| ページ | 409-16 |
| 公開日 | 2010-6-1 |
| DOI | 10.1016/j.ygyno.2010.03.004 |
| PII | S0090-8258(10)00217-9 |
| PMID | 20359736 |
| MeSH | Adenocarcinoma / genetics Adenocarcinoma / metabolism Adult Aged Aged, 80 and over Animals Calcium-Binding Proteins / metabolism Carcinoma, Squamous Cell / genetics Carcinoma, Squamous Cell / metabolism* Cell Line, Tumor DNA Copy Number Variations DNA-Binding Proteins / metabolism Female Gene Knockdown Techniques Humans Immunohistochemistry In Situ Hybridization, Fluorescence / methods Intercellular Signaling Peptides and Proteins / metabolism Jagged-1 Protein Membrane Proteins / metabolism Mice Mice, Inbred BALB C Mice, Nude Middle Aged Pre-B-Cell Leukemia Transcription Factor 1 Proto-Oncogene Proteins / metabolism RNA, Small Interfering / administration & dosage RNA, Small Interfering / genetics Receptor, Notch3 Receptors, Notch / biosynthesis* Receptors, Notch / genetics Retrospective Studies Serrate-Jagged Proteins Treatment Outcome Uterine Cervical Dysplasia / genetics Uterine Cervical Dysplasia / metabolism Uterine Cervical Neoplasms / genetics Uterine Cervical Neoplasms / metabolism* |
| IF | 4.623 |
| 引用数 | 29 |
| WOS 分野 | OBSTETRICS & GYNECOLOGY ONCOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | ME-180(RCB2106) Ca Ski(RCB1947) |