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

Overview

Journal Cancer Cell

Publisher Cell Press

Specialty Oncology

Date 2009 Nov 3

PMID 19878873

Citations 82

Authors

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 Jr

Archana Bommi-Reddy

Affiliations

Soon will be listed here.

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.

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