2009 Fiscal Year Final Research Report

Activation of hypoxia-inducible factor 1 by Human Papillomavirus Oncoproteins

Research Project

Project/Area Number	20791138
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Single-year Grants
Research Field	Obstetrics and gynecology
Research Institution	Kanazawa University
Principal Investigator	NAKAMURA Mitsuhiro Kanazawa University, 附属病院, 医員 (50377397)
Project Period (FY)	2008 – 2009
Keywords	HPV / 低酸素 / 子宮頸癌 / HIF-1
Research Abstract	Our studies indicate that cells containing complete HPV31 genomes showed enhanced levels of HIF-1α upon treatment with the hypoxia mimic DFO, which resulted from protein stabilization and led to increased expression of VEGF. Both HPV E6 and E7 were able independently to enhance induction of HIF-1α upon DFO treatment. Our studies further indicate that HPV31 E7 associates with both HIF-1α and p53 in cells, and this association results in reduced interaction of the HIF-1α/p53 complex with MDM2. These findings shed light on mechanisms by which HPV contributes to angiogenesis both in benign cervical lesions and in cervical cancers and describes a novel role of the E7 oncogene in the virus-host interaction.