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Ras-dependent induction of HIF-1α785 via the Raf/MEK/ERK pathway: a novel mechanism of Ras-mediated tumor promotion

Oncogene volume 23, pages 9427–9431 (2004)Cite this article

Abstract

Hypoxia-inducible factor-1alpha (HIF-1α) plays crucial roles in tumor promotion by transactivating approximately 60 kinds of its target genes. Recently, we reported a novel splice variant HIF-1α785, which is regulated primarily by phorbol ester. This variant can be stabilized under normoxic conditions because it loses an acetylation site Lys532. Its expression was found to promote xenografted tumor growth in nude mice. We here found that the Ras oncogene regulates HIF-1α785 expression via the Raf/MEK/ERK pathway, and that both phorbol ester and epidermal growth factor also induced HIF-1α785 via the same pathway. We also identified the nonhypoxic regulatory domain responsible for phorbol ester-induced HIF-1α785 expression. These results imply that HIF-1α785 may play an important role in tumor promotion mediated by the Ras oncogene, phorbol ester or tumor growth factors.

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Acknowledgements

This work was supported by a grant from the Korea Science and Engineering Foundation (R01-2000-000-00139-0) and by a grant from the Cancer Research Institute Seoul National University (2003).

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  1. Ji-Hong Lim and Eun-Seo Lee: These two authors contributed equally to this work

Authors and Affiliations

  1. Human Genome Research Institute and Cancer Research Institute, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul, 110-799, Korea

    Ji-Hong Lim, Eun-Seo Lee, Jung Weon Lee & Yang-Sook Chun

  2. Department of Pharmacology, Chosun University College of Medicine, 375 Seusuk-dong, Kwangju, 501-759, Korea

    Ho-Jin You

  3. Department of Pharmacology, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul, 110-799, Korea

    Jong-Wan Park

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  1. Ji-Hong Lim
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Correspondence to Yang-Sook Chun.

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Lim, JH., Lee, ES., You, HJ. et al. Ras-dependent induction of HIF-1α785 via the Raf/MEK/ERK pathway: a novel mechanism of Ras-mediated tumor promotion. Oncogene 23, 9427–9431 (2004). https://doi.org/10.1038/sj.onc.1208003

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