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NADPH oxidase 5 (NOX5)—induced reactive oxygen signaling modulates normoxic HIF‐1α and p27(Kip1) expression in malignant melanoma and other human tumors
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 o...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5675809/ https://www.ncbi.nlm.nih.gov/pubmed/28762556 http://dx.doi.org/10.1002/mc.22708 |
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author | Antony, Smitha Jiang, Guojian Wu, Yongzhong Meitzler, Jennifer L. Makhlouf, Hala R. Haines, Diana C. Butcher, Donna Hoon, Dave S. Ji, Jiuping Zhang, Yiping Juhasz, Agnes Lu, Jiamo Liu, Han Dahan, Iris Konate, Mariam Roy, Krishnendu K. Doroshow, James H. |
author_facet | Antony, Smitha Jiang, Guojian Wu, Yongzhong Meitzler, Jennifer L. Makhlouf, Hala R. Haines, Diana C. Butcher, Donna Hoon, Dave S. Ji, Jiuping Zhang, Yiping Juhasz, Agnes Lu, Jiamo Liu, Han Dahan, Iris Konate, Mariam Roy, Krishnendu K. Doroshow, James H. |
author_sort | Antony, Smitha |
collection | PubMed |
description | 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(Kip1) expression. Similarly, increased normoxic HIF‐1α expression and decreased p27(Kip1) 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‐1α expression, and increased p27(Kip1) expression. Likewise, in an additional human melanoma cell line, WM852, and in PC‐3 cells, transient knockdown of endogenous NOX5 resulted in increased p27(Kip1) and decreased HIF‐1α expression. Knockdown of endogenous NOX5 in UACC‐257 cells resulted in decreased Akt and GSK3β phosphorylation, signaling pathways known to modulate p27(Kip1) 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‐1α and networks that signal through Akt/GSK3β/p27(Kip1). |
format | Online Article Text |
id | pubmed-5675809 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-56758092018-08-16 NADPH oxidase 5 (NOX5)—induced reactive oxygen signaling modulates normoxic HIF‐1α and p27(Kip1) expression in malignant melanoma and other human tumors Antony, Smitha Jiang, Guojian Wu, Yongzhong Meitzler, Jennifer L. Makhlouf, Hala R. Haines, Diana C. Butcher, Donna Hoon, Dave S. Ji, Jiuping Zhang, Yiping Juhasz, Agnes Lu, Jiamo Liu, Han Dahan, Iris Konate, Mariam Roy, Krishnendu K. Doroshow, James H. Mol Carcinog Articles 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(Kip1) expression. Similarly, increased normoxic HIF‐1α expression and decreased p27(Kip1) 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‐1α expression, and increased p27(Kip1) expression. Likewise, in an additional human melanoma cell line, WM852, and in PC‐3 cells, transient knockdown of endogenous NOX5 resulted in increased p27(Kip1) and decreased HIF‐1α expression. Knockdown of endogenous NOX5 in UACC‐257 cells resulted in decreased Akt and GSK3β phosphorylation, signaling pathways known to modulate p27(Kip1) 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‐1α and networks that signal through Akt/GSK3β/p27(Kip1). John Wiley and Sons Inc. 2017-08-30 2017-12 /pmc/articles/PMC5675809/ /pubmed/28762556 http://dx.doi.org/10.1002/mc.22708 Text en © 2017 The Authors. Molecular Carcinogenesis Published by Wiley Periodicals, Inc. This is an Open Access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Articles Antony, Smitha Jiang, Guojian Wu, Yongzhong Meitzler, Jennifer L. Makhlouf, Hala R. Haines, Diana C. Butcher, Donna Hoon, Dave S. Ji, Jiuping Zhang, Yiping Juhasz, Agnes Lu, Jiamo Liu, Han Dahan, Iris Konate, Mariam Roy, Krishnendu K. Doroshow, James H. NADPH oxidase 5 (NOX5)—induced reactive oxygen signaling modulates normoxic HIF‐1α and p27(Kip1) expression in malignant melanoma and other human tumors |
title | NADPH oxidase 5 (NOX5)—induced reactive oxygen signaling modulates normoxic HIF‐1α and p27(Kip1) expression in malignant melanoma and other human tumors |
title_full | NADPH oxidase 5 (NOX5)—induced reactive oxygen signaling modulates normoxic HIF‐1α and p27(Kip1) expression in malignant melanoma and other human tumors |
title_fullStr | NADPH oxidase 5 (NOX5)—induced reactive oxygen signaling modulates normoxic HIF‐1α and p27(Kip1) expression in malignant melanoma and other human tumors |
title_full_unstemmed | NADPH oxidase 5 (NOX5)—induced reactive oxygen signaling modulates normoxic HIF‐1α and p27(Kip1) expression in malignant melanoma and other human tumors |
title_short | NADPH oxidase 5 (NOX5)—induced reactive oxygen signaling modulates normoxic HIF‐1α and p27(Kip1) expression in malignant melanoma and other human tumors |
title_sort | nadph oxidase 5 (nox5)—induced reactive oxygen signaling modulates normoxic hif‐1α and p27(kip1) expression in malignant melanoma and other human tumors |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5675809/ https://www.ncbi.nlm.nih.gov/pubmed/28762556 http://dx.doi.org/10.1002/mc.22708 |
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