High expression of HIF-2α and its anti-radiotherapy effect in lung cancer stem cells.
Genet Mol Res
; 14(4): 18110-20, 2015 Dec 22.
Article
em En
| MEDLINE
| ID: mdl-26782458
Hypoxia-inducible factor-2 alpha (HIF-2α) has been shown to regulate cell stemness, although the expression and effects of HIF-2α in lung cancer stem cells remained unclear. This study investigated HIF-2α expression in lung cancer stem cells, as well as the relationship between HIF-2α expression and radioresistance in lung cancer cells. Stem-like cells (CD133(+)) in the non-small-cell lung cancer cell line A549 were enriched by serum-free culture conditions, and CD133(+) cells were sorted via fluorescence-activated cell sorting. A549 cells were treated with middle-infrared radiation, and the level of HIF-2α expression was determined by a quantitative polymerase chain reaction assay and western blot analysis. The level of HIF-2α expression in tissue sections from 50 cases of clinically confirmed non-small-cell lung cancer was determined via immunohistochemical analysis, and its correlation with prognosis after radiotherapy was analyzed. HIF-2α levels in CD133(+) cells were significantly higher than those in CD133(-) cells (P = 0.032). However, after radiation treatment, these levels were significantly upregulated in both CD133(+) and CD133(-) cells (P = 0.031 and P = 0.023, respectively). After irradiation, the proportions of apoptotic, dead, and autophagic CD133(+) A549 cells were considerably lower than those of CD133(-) A549 cells (P < 0.05). Furthermore, the recovery of carcinoembryonic antigen to pre-radiation levels was more rapid in lung cancer patients with high levels of HIF-2α expression, and these patients had shorter survival times (P = 0.018). HIF-2α is highly expressed in lung cancer stem cells, which may lead to radioresistance. In conclusion, HIF-2α is a potential prognostic marker for lung cancer.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tolerância a Radiação
/
Biomarcadores Tumorais
/
Carcinoma Pulmonar de Células não Pequenas
/
Fatores de Transcrição Hélice-Alça-Hélice Básicos
Tipo de estudo:
Prognostic_studies
Limite:
Female
/
Humans
/
Male
Idioma:
En
Revista:
Genet Mol Res
Assunto da revista:
BIOLOGIA MOLECULAR
/
GENETICA
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
China
País de publicação:
Brasil