Tumorigenic Role of Orphan Nuclear Receptor NR0B1 in Lung Adenocarcinoma
AUTOR(ES)
Oda, Tomofumi
FONTE
American Society for Investigative Pathology
RESUMO
Cancer stem cells are a limited population of tumor cells that are thought to reconstitute whole tumors. The Hoechst dye exclusion assay revealed that tumors are composed of both a main population and a side population of cells, which are rich in cancer stem cells. NR0B1 is an orphan nuclear receptor that is expressed to a greater extent in the side population, as compared with the main population, of a lung adenocarcinoma cell line. In this study, we investigated the role of NR0B1 in lung adenocarcinoma cells. Reduction of NR0B1expression levels in lung adenocarcinoma cell lines resulted in vulnerability to anti-cancer drugs and decreased abilities for invasion, in vitro colony formation, and tumorigenicity in non-obese diabetic/severe compromised immunodeficient mice. When 193 cases of lung adenocarcinoma were immunohistochemically examined, higher levels of NR0B1 expression correlated with higher rates of lymph node metastasis and recurrence. Multivariate analysis revealed high NR0B1 expression levels, stage of the disease, and size of tumor to be independent unfavorable prognostic factors for overall and disease-free survival rates. In clinical samples, NR0B1 expression levels inversely correlated to the proportion of methylated CpG sequences around the transcription initiation site of the NR0B1 gene, suggesting the epigenetic control of NR0B1 transcription in lung adenocarcinoma. In conclusion, NR0B1 might play a role in the malignant potential of lung adenocarcinoma.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2731142Documentos Relacionados
- X-linked adrenal hypoplasia congenita: clinical and follow-up findings of two kindreds, one with a novel NR0B1 mutation
- Microssatélites (GGAA)n no promotor do gene NR0B1 em pacientes afetados e não afetados pelo sarcoma de Ewing
- TIF1β/KAP-1 Is a Coactivator of the Orphan Nuclear Receptor NGFI-B/Nur77*S⃞
- Transcriptional activation by the orphan nuclear receptor ARP-1.
- Insuficiência adrenal leve causada por mutação do gene NR0B1 (DAX1) em menino com uma associação de hipogonadismo hipogonadotrófico, baixa estatura final e transtorno de déficit de atenção