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HIF-2alpha Knockdown in A498 (VHL-/-) ccRCC cells

ABSTRACT: HIF-2alpha is essential for (VHL-/-) ccRCC subcutaneous tumor growth in mice, and in tumor cell lines, its inhibition results in increased ROS accumulation, tumor cell death and responsiveness to radiation treatment. We have utilized transcriptional profiling to screen for putative HIF-2alpha targets genes that serve an anti-oxidant and, thus, cell survival function. A498 ccRCC cell line was treated with control siRNA or mixture of two HIF-2alpha specific siRNA for 48 hours, and RNA was harvested. 4 independent experiments were performed, and expression was compared between control and HIF-2alpha knockdown groups. 8 total samples were applied to Affymetrix Human Gene 1.0 ST Arrays. We performed two-class paired analysis using Significance Analysis of Microarrays (SAM) software to compare expression in the CT (control siRNA) and H2 (Hif2-alpha siRNA) groups.

ORGANISM(S): Homo sapiens

SUBMITTER: Amar Majmundar 

PROVIDER: E-GEOD-16622 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

HIF2alpha inhibition promotes p53 pathway activity, tumor cell death, and radiation responses.

Bertout Jessica A JA   Majmundar Amar J AJ   Gordan John D JD   Lam Jennifer C JC   Ditsworth Dara D   Keith Brian B   Brown Eric J EJ   Nathanson Katherine L KL   Simon M Celeste MC  

Proceedings of the National Academy of Sciences of the United States of America 20090812 34

Approximately 50% of cancer patients receive radiation treatment, either alone or in combination with other therapies. Tumor hypoxia has long been associated with resistance to radiation therapy. Moreover, the expression of hypoxia inducible factors HIF1alpha and/or HIF2alpha correlates with poor prognosis in many tumors. Recent evidence indicates that HIF1alpha expression can enhance radiation-induced apoptosis in cancer cells. We demonstrate here that HIF2alpha inhibition promotes tumor cell d  ...[more]

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