Increased Nox1 and hydrogen peroxide in prostate cancer.
BACKGROUND
Reactive oxygen species (ROS) are emerging as candidate mediators of growth and angiogenesis in cancer. Increased ROS often correlates with cell growth, e.g., Ras-transformed cells and cells treated with growth factors. While non-transformed cells respond to growth factors/cytokines with the regulated production of ROS, tumor cells in culture frequently overproduce H(2)O(2). We propose that NADPH oxidases (Nox) account for increased levels of ROS in some cancers. Previously, transfection of Nox1 into a prostate cancer cell line dramatically enhanced tumor growth (Arbiser et al.: PNAS 99:715-720, 2001).


METHODS
Using immunohistochemistry, immunofluorescence, dihydroethidium staining, and Flow cytometry, we investigated the correlation between Nox1 and ROS in prostate cancer.


RESULTS
Here, we demonstrate that human prostate tumors show increased H(2)O(2) levels. Furthermore, 80% of human prostate tumor samples show markedly increased Nox1 protein levels and increased mRNA levels. In addition, a series of cell lines developed from LNCaP prostate cancer cells that demonstrate increasing tumor and metastatic potential, show increased Nox1 and a parallel increase in H(2)O(2) levels.


CONCLUSIONS
The results illustrate that human prostate cancer frequently show both increased H(2)O(2) and Nox1, and that in an animal model system increased Nox1/H(2)O(2) correlates with increased tumorigenicity.
Lim
So Dug
SD
Department of Pathology and Laboratory Medicine, Emory Clinic Building B, Emory University School of Medicine, Atlanta, Georgia, USA.
Sun
Carrie
C
Lambeth
J David
JD
Marshall
Fray
F
Amin
Mahul
M
Chung
Leland
L
Petros
John A
JA
Arnold
Rebecca S
RS
D000818:Animals; D019070:Cell Lineage; D015870:Gene Expression; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D008297:Male; D051379:Mice; D000074624:NADPH Oxidase 1; D019255:NADPH Oxidases / Q000235:genetics* / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000503:physiopathology / Q000556:secondary; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D000074624:NADPH Oxidase 1; D019255:NADPH Oxidases; C402799:NOX1 protein, human