Control of Cyclin D1 and Breast Tumorigenesis by the EglN2 Prolyl Hydroxylase

Qing Zhang, Jinming Gu, Lianjie Li, Jiayun Liu, Biao Luo, Hiu Wing Cheung, Jesse S. Boehm, Min Ni, Christoph Geisen, David E. Root, Kornelia Polyak, Myles Brown, Andrea L. Richardson, William C. Hahn, William G. Kaelin, Archana Bommi-Reddy

Research output: Contribution to journalArticle

88 Scopus citations

Abstract

2-Oxoglutarate-dependent dioxygenases, including the EglN prolyl hydroxylases that regulate HIF, can be inhibited with drug-like molecules. EglN2 is estrogen inducible in breast carcinoma cells and the lone Drosophila EglN interacts genetically with Cyclin D1. Although EglN2 is a nonessential gene, we found that EglN2 inactivation decreases Cyclin D1 levels and suppresses mammary gland proliferation in vivo. Regulation of Cyclin D1 is a specific attribute of EglN2 among the EglN proteins and is HIF independent. Loss of EglN2 catalytic activity inhibits estrogen-dependent breast cancer tumorigenesis and can be rescued by exogenous Cyclin D1. EglN2 depletion also impairs the fitness of lung, brain, and hematopoietic cancer lines. These findings support the exploration of EglN2 inhibitors as therapeutics for estrogen-dependent breast cancer and other malignancies.

Original languageEnglish (US)
Pages (from-to)413-424
Number of pages12
JournalCancer Cell
Volume16
Issue number5
DOIs
StatePublished - Nov 6 2009

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Keywords

  • CELLCYCLE

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

Cite this

Zhang, Q., Gu, J., Li, L., Liu, J., Luo, B., Cheung, H. W., Boehm, J. S., Ni, M., Geisen, C., Root, D. E., Polyak, K., Brown, M., Richardson, A. L., Hahn, W. C., Kaelin, W. G., & Bommi-Reddy, A. (2009). Control of Cyclin D1 and Breast Tumorigenesis by the EglN2 Prolyl Hydroxylase. Cancer Cell, 16(5), 413-424. https://doi.org/10.1016/j.ccr.2009.09.029