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Erschienen in:
01.11.2008 | Original Article
Role of Hypoxia-inducible factor-1α and Survivin in colorectal carcinoma progression
Erschienen in: International Journal of Colorectal Disease | Ausgabe 11/2008
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Background and aims
Hypoxia-inducible factor-1α (HIF-1α) is the main active subunit of HIF-1 that promoted tumor cells survival and critical steps in tumor progression and aggressiveness. The authors aimed to investigate the role of HIF-1α and Survivin in colorectal cancer (CRC) progression.
Materials and methods
Plasmid expressing small interfering RNA (siRNA) against HIF-1α was constructed and transfected into LS174T cells with Lipofectamine. The LS174T cells were incubated for 24 h under hypoxic condition. The inhibitory effects of siRNA on HIF-1α gene was determined by semiquantitative reverse transcriptase polymerase chain reaction and Western blot. Expression of HIF-1α and Survivin was investigated by immunohistochemistry in colorectal adenocarcinomas tissue microarrays.
Results
HIF-1α and Survivin expressions were markedly downregulated after the siRNA expression vector against HIF-1α was transfected into the LS174T cells. Of the eight adenoma lesions, one case (12.25%) and four cases (50%) were positive for HIF-1α and Survivin, respectively. Of the 69 cases of CRCs, 46 cases (66.7%) and 39 cases (56.5%) were positive for HIF-1α and Survivin, respectively. The positive rate of HIF-1α protein in CRCs was significantly higher than that in colorectal adenoma lesions (P < 0.05). HIF-1α protein expression was significantly higher in patients with stage III than in patients with stage I–II CRCs (P < 0.01). In addition, overexpression of HIF-1α in higher stages of CRCs was found to correlate positively with Survivin levels (P < 0.001).
Conclusions
Our data demonstrate that HIF-1α and Survivin are mostly expressed in invasive CRCs. Inhibition of HIF-1α may lead to exploration of its potential as a diagnostic tool and possibly a target for gene therapy for colorectal carcinoma.