The NAD(P)H:Quinone Oxidoreductase 1 induces cell cycle progression and proliferation of melanoma cells.
The oxidoreductase NQO1 plays a prominent role in maintaining the cellular homeostasis. NQO1 is mainly a cytosolic enzyme which catalyzes the metabolism of quinones and is present in almost all tissue types providing protection against different stresses including xenobiotics, oxidants, UV light, and ionizing radiation. This enzyme is overexpressed in many cancerous tissues and its function in carcinogenesis remains unclear. Due to the relative lack of information on the role of NQO1 in melanoma pathogenesis, we attempted to determine the expression and basic function of NQO1 in melanoma cell proliferation. We found that NQO1 is overexpressed in most melanoma cell lines with respect to melanocytes. Furthermore, the expression of this oxidoreductase significantly induces cell cycle progression by upregulating the expression of cyclins A2, B1 and D1, leading to the proliferation of melanoma cells. Our results also indicate that NQO1 is an upstream regulator of NF-kappaB p50, a factor linked to melanoma progression and poor patient prognosis. Interestingly, we found that NQO1 stabilizes the transactivator BCL3, which in turn upregulates NF-kappaB p50. More importantly, our results also indicate that NF-kappaB p50 correlates with the expression of NQO1 and mediates its role in the proliferation of melanoma cells.
Garate
Marco
M
Department of Dermatology and Skin Science, Jack Bell Research Centre, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, BC Canada.
Wani
Aijaz A
AA
Li
Gang
G
D015153:Blotting, Western; D002453:Cell Cycle / Q000502:physiology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002469:Cell Separation; D005434:Flow Cytometry; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D047468:Immunoprecipitation; D008545:Melanoma / Q000235:genetics / Q000378:metabolism*; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics / Q000378:metabolism*; D052002:NF-kappa B p50 Subunit / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
D052002:NF-kappa B p50 Subunit; D034741:RNA, Small Interfering; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human