NADPH oxidase 5 (NOX5)-induced reactive oxygen signaling modulates normoxic HIF-1α and p27

Publication Title

Molecular carcinogenesis

Authors

Smitha Antony
Guojian Jiang
Yongzhong Wu
Jennifer L Meitzler
Hala R Makhlouf
Diana C Haines
Donna Butcher
Dave S B Hoon, Department of Translational Molecular Medicine, John Wayne Cancer Institute (JWCI), Pacific Neuroscience Institute, Saint John's Health Center, Providence Health Systems, Santa Monica, CA, 90404, USAFollow
Jiuping Ji
Yiping Zhang
Agnes Juhasz
Jiamo Lu
Han Liu
Iris Dahan
Mariam Konate
Krishnendu K Roy
James H Doroshow

Document Type

Article

Publication Date

12-1-2017

Keywords

Blotting, Western; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Cyclin-Dependent Kinase Inhibitor p27; Female; Glycogen Synthase Kinase 3 beta; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Male; Melanoma; NADPH Oxidase 5; Ovarian Neoplasms; Phosphorylation; Prostatic Neoplasms; Proto-Oncogene Proteins c-akt; RNA Interference; Reactive Oxygen Species; Signal Transduction

Abstract

NADPH oxidase 5 (NOX5) generated reactive oxygen species (ROS) have been implicated in signaling cascades that regulate cancer cell proliferation. To evaluate and validate NOX5 expression in human tumors, we screened a broad range of tissue microarrays (TMAs), and report substantial overexpression of NOX5 in malignant melanoma and cancers of the prostate, breast, and ovary. In human UACC-257 melanoma cells that possesses high levels of functional endogenous NOX5, overexpression of NOX5 resulted in enhanced cell growth, increased numbers of BrdU positive cells, and increased γ-H2AX levels. Additionally, NOX5-overexpressing (stable and inducible) UACC-257 cells demonstrated increased normoxic HIF-1α expression and decreased p27

Clinical Institute

Cancer

Specialty/Research Institute

Oncology