Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Control of cyclin D1 and breast tumorigenesis by the EglN2 prolyl hydroxylase.

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.

Pubmed ID: 19878873


  • 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


Cancer cell

Publication Data

November 6, 2009

Associated Grants

  • Agency: NCI NIH HHS, Id: 5R01CA068490-14
  • Agency: NCI NIH HHS, Id: F32 CA139929
  • Agency: NCI NIH HHS, Id: K99 CA160351
  • Agency: NCI NIH HHS, Id: R00 CA160351
  • Agency: NCI NIH HHS, Id: R01 CA068490
  • Agency: NCI NIH HHS, Id: R01 CA068490-14
  • Agency: Howard Hughes Medical Institute, Id:
  • Agency: Howard Hughes Medical Institute, Id:

Mesh Terms

  • Animals
  • Breast Neoplasms
  • Cell Culture Techniques
  • Cell Line, Tumor
  • Cyclin D1
  • Dioxygenases
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic
  • HeLa Cells
  • Humans
  • Immunoblotting
  • Mice
  • Mice, Transgenic
  • Procollagen-Proline Dioxygenase
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transfection