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

82 Citations (Scopus)

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

Fingerprint

Prolyl Hydroxylases
Cyclin D1
Carcinogenesis
Breast
Estrogens
Breast Neoplasms
Dioxygenases
Human Mammary Glands
Brain Neoplasms
Drosophila
Lung
Pharmaceutical Preparations
Genes
Neoplasms
Proteins

Keywords

  • CELLCYCLE

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Oncology

Cite this

Zhang, Q., Gu, J., Li, L., Liu, J., Luo, B., Cheung, H. W., ... 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

Control of Cyclin D1 and Breast Tumorigenesis by the EglN2 Prolyl Hydroxylase. / Zhang, Qing; Gu, Jinming; Li, Lianjie; Liu, Jiayun; Luo, Biao; Cheung, Hiu Wing; Boehm, Jesse S.; Ni, Min; Geisen, Christoph; Root, David E.; Polyak, Kornelia; Brown, Myles; Richardson, Andrea L.; Hahn, William C.; Kaelin, William G.; Bommi-Reddy, Archana.

In: Cancer Cell, Vol. 16, No. 5, 06.11.2009, p. 413-424.

Research output: Contribution to journalArticle

Zhang, Q, Gu, J, Li, L, Liu, J, Luo, B, Cheung, HW, Boehm, JS, Ni, M, Geisen, C, Root, DE, Polyak, K, Brown, M, Richardson, AL, Hahn, WC, Kaelin, WG & Bommi-Reddy, A 2009, 'Control of Cyclin D1 and Breast Tumorigenesis by the EglN2 Prolyl Hydroxylase', Cancer Cell, vol. 16, no. 5, pp. 413-424. https://doi.org/10.1016/j.ccr.2009.09.029
Zhang, Qing ; Gu, Jinming ; Li, Lianjie ; Liu, Jiayun ; Luo, Biao ; Cheung, Hiu Wing ; Boehm, Jesse S. ; Ni, Min ; Geisen, Christoph ; Root, David E. ; Polyak, Kornelia ; Brown, Myles ; Richardson, Andrea L. ; Hahn, William C. ; Kaelin, William G. ; Bommi-Reddy, Archana. / Control of Cyclin D1 and Breast Tumorigenesis by the EglN2 Prolyl Hydroxylase. In: Cancer Cell. 2009 ; Vol. 16, No. 5. pp. 413-424.
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