期刊
FREE RADICAL BIOLOGY AND MEDICINE
卷 51, 期 9, 页码 1717-1726出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2011.07.025
关键词
Heme oxygenase-1; Carcinogenesis; Squamous cell carcinoma; DMBA; Inflammation; Oxidative stress; Free radicals
资金
- Ministry of Science and Higher Education [N301 08032/3156, N301 144336, 347/N-INCA/2008, 311/N-COST/2008]
- Wellcome Trust
- Foundation for Polish Science
- European Union [POIG.02.01.00-12-064/08, 02.02.00-00-014/08, 01.02-00-109/09, 01.02.00-069/09]
Heme oxygenase-1 (HO-1) is an antioxidative and cytoprotective enzyme, which may protect neoplastic cells against anticancer therapies, thereby promoting the progression of growing tumors. Our aim was to investigate the role of HO-1 in cancer induction. Experiments were performed in HO-1(+/+), HO-1(+/-), and HO-1(-/-) mice subjected to chemical induction of squamous cell carcinoma with 7,12-dimethylbenz[a]anthracene and phorbol 12-myristate 13-acetate. Measurements of cytoprotective genes in the livers evidenced systemic oxidative stress in the mice of all the HO-1 genotypes. Carcinogen-induced lesions appeared earlier in HO-1(-/-) and HO-1(+/-) than in wild-type animals. They also contained much higher concentrations of vascular endothelial growth factor and keratinocyte chemoattractant, but lower levels of tumor necrosis factor-alpha and interleukin-12. Furthermore, tumors grew much larger in HO-1 knockouts than in the other groups, which was accompanied by an increased rate of animal mortality. However, pathomorphological analysis indicated that HO-1(-/-) lesions were mainly large but benign papillomas. In contrast, in mice expressing HO-1, most lesions displayed dysplastic features and developed to invasive carcinoma. Thus, HO-1 may protect healthy tissues against carcinogen-induced injury, but in already growing tumors it seems to favor their progression toward more malignant forms. (C) 2011 Elsevier Inc. All rights reserved.
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