title: Effects of heme oxygenase-1 on induction and development of chemically induced squamous cell carcinoma in mice.
abstract: 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-α 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.
authors.affiliation: Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics, and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Krakow, Poland.
authors.forename: Halina
authors.initials: H
authors.lastname: Was
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Sokolowska
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Sierpniowska
authors.forename: Paweł
authors.initials: P
authors.lastname: Dominik
authors.forename: Klaudia
authors.initials: K
authors.lastname: Skrzypek
authors.forename: Bozena
authors.initials: B
authors.lastname: Lackowska
authors.forename: Antoni
authors.initials: A
authors.lastname: Pratnicki
authors.forename: Anna
authors.initials: A
authors.lastname: Grochot-Przeczek
authors.forename: Hevidar
authors.initials: H
authors.lastname: Taha
authors.forename: Jerzy
authors.initials: J
authors.lastname: Kotlinowski
authors.forename: Magdalena
authors.initials: M
authors.lastname: Kozakowska
authors.forename: Andrzej
authors.initials: A
authors.lastname: Mazan
authors.forename: Witold
authors.initials: W
authors.lastname: Nowak
authors.forename: Lucie
authors.initials: L
authors.lastname: Muchova
authors.forename: Libor
authors.initials: L
authors.lastname: Vitek
authors.forename: Anna
authors.initials: A
authors.lastname: Ratajska
authors.forename: Jozef
authors.initials: J
authors.lastname: Dulak
authors.forename: Alicja
authors.initials: A
authors.lastname: Jozkowicz
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced* / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D051547:Heme Oxygenase-1 / Q000172:deficiency / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D012878:Skin Neoplasms / Q000139:chemically induced* / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives
chemical_list: C016658:phorbolol myristate acetate; D015127:9,10-Dimethyl-1,2-benzanthracene; D051547:Heme Oxygenase-1; D013755:Tetradecanoylphorbol Acetate