@article{3fea653b08cd48e6a25e68ff5718feb0,
title = "Control of Cyclin D1 and Breast Tumorigenesis by the EglN2 Prolyl Hydroxylase",
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.",
keywords = "CELLCYCLE",
author = "Qing Zhang and Jinming Gu and Lianjie Li and Jiayun Liu and Biao Luo and Cheung, {Hiu Wing} and Boehm, {Jesse S.} and Min Ni and Christoph Geisen and Root, {David E.} and Kornelia Polyak and Myles Brown and Richardson, {Andrea L.} and Hahn, {William C.} and Kaelin, {William G.} and Archana Bommi-Reddy",
note = "Funding Information: We thank Regeneron Pharmaceuticals for the EglN2 −/ − mice, Oliver Hankinson for the ARNT − /− cells, Silvia Giordano for the inducible shRNA vector, Yan Geng for help with mammary gland analysis, Margaret McLaughlin-Drubin for help with E7 immunoblots, Mariela Jaskelioff for help with xenograft studies, and members of the Kaelin Laboratory for useful discussions. This work was supported by National Cancer Institute Dana-Farber/Harvard SPORE in Breast Cancer (A.L.R.) and the Breast Cancer Research Foundation (A.L.R. and W.G.K.). Q.Z. is supported by a postdoctoral fellowship from Terri Brodeur Breast Cancer Foundation. W.G.K. is a Howard Hughes Medical Institute Investigator and a Doris Duke Distinguished Clinical Investigator. This work is supported in part by a National Institutes of Health grant (5R01CA068490-14) to W.G.K. W.G.K. owns equity in Fibrogen, Inc., which is developing prolyl hydroxylase inhibitors as potential therapeutics. ",
year = "2009",
month = nov,
day = "6",
doi = "10.1016/j.ccr.2009.09.029",
language = "English (US)",
volume = "16",
pages = "413--424",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "5",
}