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2017 ; 13
(ä): 182-195
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Decoding NADPH oxidase 4 expression in human tumors
#MMPMID28578276
Meitzler JL
; Makhlouf HR
; Antony S
; Wu Y
; Butcher D
; Jiang G
; Juhasz A
; Lu J
; Dahan I
; Jansen-Dürr P
; Pircher H
; Shah AM
; Roy K
; Doroshow JH
Redox Biol
2017[Oct]; 13
(ä): 182-195
PMID28578276
show ga
NADPH oxidase 4 (NOX4) is a redox active, membrane-associated protein that
contributes to genomic instability, redox signaling, and radiation sensitivity in
human cancers based on its capacity to generate H(2)O(2) constitutively. Most
studies of NOX4 in malignancy have focused on the evaluation of a small number of
tumor cell lines and not on human tumor specimens themselves; furthermore, these
studies have often employed immunological tools that have not been well
characterized. To determine the prevalence of NOX4 expression across a broad
range of solid tumors, we developed a novel monoclonal antibody that recognizes a
specific extracellular region of the human NOX4 protein, and that does not
cross-react with any of the other six members of the NOX gene family. Evaluation
of 20 sets of epithelial tumors revealed, for the first time, high levels of NOX4
expression in carcinomas of the head and neck (15/19 patients), esophagus (12/18
patients), bladder (10/19 patients), ovary (6/17 patients), and prostate (7/19
patients), as well as malignant melanoma (7/15 patients) when these tumors were
compared to histologically-uninvolved specimens from the same organs. Detection
of NOX4 protein upregulation by low levels of TGF-?1 demonstrated the sensitivity
of this new probe; and immunofluorescence experiments found that high levels of
endogenous NOX4 expression in ovarian cancer cells were only demonstrable
associated with perinuclear membranes. These studies suggest that NOX4 expression
is upregulated, compared to normal tissues, in a well-defined, and specific group
of human carcinomas, and that its expression is localized on intracellular
membranes in a fashion that could modulate oxidative DNA damage.
|*Gene Expression Regulation, Neoplastic
[MESH]
|Carcinoma/genetics/metabolism
[MESH]
|Cell Line, Tumor
[MESH]
|Esophageal Neoplasms/genetics/metabolism
[MESH]
|Female
[MESH]
|HEK293 Cells
[MESH]
|Head and Neck Neoplasms/genetics/metabolism
[MESH]