11Beta-hydroxysteroid dehydrogenase 1 expression in squamous cell carcinomas of the head and neck.
11Beta-hydroxysteroid dehydrogenase 1 (11beta-HSD1) has been identified as a major detoxification enzyme of one of the most potent tobacco smoke-derived carcinogens, NNK. If not metabolized by 11beta-HSD1, activation of NNK by cytochrome p450 mono-oxidase 2D6 (CYP2D6) results in an electrophile intermediate responsible for DNA damage. Interindividual variability in the expression of 11beta-HSD1 and CYP2D6 has been found to influence the susceptibility to lung cancer. The aim of this study was to compare 11beta-HSD1 mRNA expression and CYP2D6 metabolizer status in pharyngeal tissues of patients with oropharyngeal carcinoma and controls. In 20 patients with oropharyngeal cancer and 15 non-smoking controls, the 11beta-HSD1 mRNA expression was assessed with RT-PCR. The frequency of genetic polymorphisms of the CYP2D6 gene was assessed using RFLP. It was found that 11beta-HSD1 mRNA is expressed in human pharyngeal mucosa. It is upregulated in mucosa exposed to tobacco smoke. In tumour tissues, 11beta-HSD1 expression was significantly lower than in non-affected mucosa. The frequency distribution of CYP2D6 gene polymorphisms was similar in patients and controls. Chronic tobacco abuse results in 11beta-HSD1 enzyme induction. A reduction of 11beta-HSD1 expression in tumour tissues could be a consequence of malignantly transformed cells. It remains unclear if the lower 11beta-HSD1 expression gives rise to an increased rate of additional mutations.
Gronau
S
S
Department of Otorhinolaryngology, University of Ulm, Germany. silke.gronau@medizin.uni-ulm.de
Koenig Greger
D
D
Jerg
M
M
Riechelmann
H
H
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D002294:Carcinoma, Squamous Cell / Q000201:enzymology*; D019389:Cytochrome P-450 CYP2D6 / Q000378:metabolism; D006801:Humans; D006913:Hydroxysteroid Dehydrogenases / Q000032:analysis* / Q000235:genetics; D009959:Oropharyngeal Neoplasms / Q000201:enzymology*; D010614:Pharynx / Q000201:enzymology; D012150:Polymorphism, Restriction Fragment Length; D012333:RNA, Messenger / Q000032:analysis; D012907:Smoking / Q000378:metabolism
D012333:RNA, Messenger; D006913:Hydroxysteroid Dehydrogenases; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; C468386:HSD11B1 protein, human; D019389:Cytochrome P-450 CYP2D6