Unknown

Dataset Information

0

NADPH oxidase 5 (NOX5)-induced reactive oxygen signaling modulates normoxic HIF-1? and p27Kip1 expression in malignant melanoma and other human tumors.


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 ?-H2AX levels. Additionally, NOX5-overexpressing (stable and inducible) UACC-257 cells demonstrated increased normoxic HIF-1? expression and decreased p27Kip1 expression. Similarly, increased normoxic HIF-1? expression and decreased p27Kip1 expression were observed in stable NOX5-overexpressing clones of KARPAS 299 human lymphoma cells and in the human prostate cancer cell line, PC-3. Conversely, knockdown of endogenous NOX5 in UACC-257 cells resulted in decreased cell growth, decreased HIF-1? expression, and increased p27Kip1 expression. Likewise, in an additional human melanoma cell line, WM852, and in PC-3 cells, transient knockdown of endogenous NOX5 resulted in increased p27Kip1 and decreased HIF-1? expression. Knockdown of endogenous NOX5 in UACC-257 cells resulted in decreased Akt and GSK3? phosphorylation, signaling pathways known to modulate p27Kip1 levels. In summary, our findings suggest that NOX5 expression in human UACC-257 melanoma cells could contribute to cell proliferation due, in part, to the generation of high local concentrations of extracellular ROS that modulate multiple pathways that regulate HIF-1? and networks that signal through Akt/GSK3?/p27Kip1 .

SUBMITTER: Antony S 

PROVIDER: S-EPMC5675809 | BioStudies | 2017-01-01

REPOSITORIES: biostudies

Similar Datasets

2013-01-01 | S-EPMC3859815 | BioStudies
2016-01-01 | S-EPMC5058623 | BioStudies
1000-01-01 | S-EPMC3260799 | BioStudies
2012-01-01 | S-EPMC3335157 | BioStudies
1000-01-01 | S-EPMC2909981 | BioStudies
2019-12-31 | GSE112553 | GEO
2020-01-01 | S-EPMC7232248 | BioStudies
2013-01-01 | S-EPMC3747959 | BioStudies
2017-01-01 | S-EPMC5469354 | BioStudies
2020-01-01 | S-EPMC7393205 | BioStudies