Arginase 2 and nitric oxide synthase: Pathways associated with the pathogenesis of thyroid tumors

Autor(es)

Sousa, Maria Sharmila A. ^{[1, 2]} ; Latini, Flavia R. M. ^{[1, 2]} ; Monteiro, Hugo P. ^[3] ; Cerutti, Janete M. ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Div Endocrinol, Dept Med, BR-04039032 Sao Paulo - Brazil

^[2] Univ Fed Sao Paulo, Genet Basis Thyroid Tumors Lab, Div Genet, Dept Morphol & Genet, BR-04039032 Sao Paulo - Brazil

^[3] Univ Fed Sao Paulo, Interdisciplinary Ctr Gene Therapy, Dept Biochem, BR-04039032 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Free Radical Biology and Medicine; v. 49, n. 6, p. 997-1007, SEP 15 2010.
• Citações Web of Science: 12

Resumo

We have previously shown that ARG2 expression was increased in most malignant thyroid tumors, but absent in benign lesions and normal tissues. Small interfering RNA knockdown was used to investigate the role of ARG2 in a thyroid carcinoma cell line. ARG2 knockdown decreased eNOS expression as well as the expression of eNOS-related genes (p21, Akt1, HIF-1, VEGF, and CAVI). ARG2 silencing changed tumor properties of thyroid cancer cells promoting apoptosis and reduced expression of cell proliferation markers. These results, coupled with enhanced nitric oxide production and elevated reactive oxygen species (ROS) levels, account for the altered intracellular redox environment. Genes related to either production (DUOX1 and NOX4) or catabolism (SODS) of ROS and reactive nitrogen species were negatively modulated by ARG2 knockdown. Additionally, a positive correlation of ARG2 with eNOS and related genes was investigated in thyroid tumors, further substantiating our in vitro findings. Our results suggest that ARG2 and eNOS may work in a coordinated manner and the underlying mechanism might be of major significance for thyroid tumorigenesis and/or tumor progression pathways. Fine modulation of ARG2, eNOS, and related genes may represent a potential source for targeted therapy of several cancer types. (C) 2010 Elsevier Inc. All rights reserved. (AU)

• Processo FAPESP: 05/60330-8 - Marcadores moleculares no diagnóstico e prognóstico de pacientes com tumores da tiroide humana: transição da pesquisa básica para a clínica
• Beneficiário: Janete Maria Cerutti
• Linha de fomento: Auxílio à Pesquisa - Temático
• Processo FAPESP: 09/11257-7 - Análise do Papel da Arginase II (ARG2) na Patogênese dos Tumores da Tiróide
• Beneficiário: Janete Maria Cerutti
• Linha de fomento: Auxílio à Pesquisa - Regular