Biological role and prognostic significance of NAC1 in ovarian cancer
| Autor: | Munmun Rahman, Shamima Yeasmin, Atsuko Katagiri, Kohji Miyazaki, Kouji Iida, Masako Ishikawa, Naomi Nakayama, Kentaro Nakayama, Mohammed Tanjimur Rahman |
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| Rok vydání: | 2010 |
| Předmět: |
Pathology
medicine.medical_specialty Mice Nude Cell Growth Processes Transfection Disease-Free Survival Histone Deacetylases Mice chemistry.chemical_compound Cell Movement Cell Line Tumor Biomarkers Tumor medicine Animals Humans Gene silencing Neoplasm Invasiveness Neoplasm Staging Ovarian Neoplasms Mice Inbred BALB C Gene knockdown medicine.diagnostic_test Cell growth business.industry Gene Amplification Obstetrics and Gynecology Middle Aged medicine.disease Neoplasm Proteins Repressor Proteins Serous fluid Oncology chemistry Gene Knockdown Techniques Cancer cell Disease Progression Cancer research Female Growth inhibition Ovarian cancer business Fluorescence in situ hybridization |
| Zdroj: | Gynecologic Oncology. 119:469-478 |
| ISSN: | 0090-8258 |
| Popis: | Objective This study examined the biological and clinical significance of NAC1 expression in ovarian cancer and assessed whether NAC1 has the potential to be a therapeutic target. Methods NAC1 expression and gene amplification were assessed in ovarian cancers by immunohistochemistry, fluorescence in situ hybridization, and clinical data collected by a retrospective chart review. NAC1 gene knockdown using silencing RNA and a NAC1 gene transfection system were used to assess NAC1 function in ovarian cancer tissue samples. Results The frequency of positive NAC1 expression in serous adenocarcinomas (50.0%:22/44) was significantly higher than that in the other histological subtypes (33.3%: 10/30). NAC1 gene amplification was identified in seven (9.5%) of 74 ovarian carcinomas. Positive NAC1 expression significantly correlated with shorter disease-free and overall survival ( P =0.002, P =0.0048). A multivariate analysis showed that positive NAC1 expression was an independent prognostic factor for disease-free and overall survival after standard platinum–taxane chemotherapy ( P =0.0027, P =0.0302). Profound growth inhibition, increased apoptosis, decreased cell proliferation, and decreased cell migration and invasion were observed in silencing RNA-treated cancer cells with NAC1 overexpression compared with cancer cells without NAC1 expression. NAC1 overexpression stimulated proliferation, migration, and invasion in ovarian cancer cell lines KF28 and TOV-21G, which normally lacked NAC1 expression. Conclusion These findings indicate that NAC1 over-expression is critical to the growth and survival of ovarian cancers. Furthermore, they suggest that NAC1 silencing RNA-induced phenotypes depend on the expression status of the targeted cell line. Therefore, NAC1-targeted therapy may benefit ovarian cancer patients with NAC1 expression. |
| Databáze: | OpenAIRE |
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