DESBRIERE, RAOUL, VINCENT VUAROQUEAUX, VINCENT ACHARD, SANDRINE BOULLU-CIOCCA, MARTIN LABUHN, ANNE DUTOUR, AND MICHEL GRINO. Increased expression of 11␤-hydroxysteroid dehydrogenase type 1 mRNA in both visceral and subcutaneous adipose tissue of obese patients. Obesity. 2006;14:794 -798. Objective: Data from rodents provide evidence for a causal role of 11␤-hydroxysteroid dehydrogenase type 1 (11␤-HSD-1) in the development of obesity and its complications. In humans, 11␤-HSD-1 is increased in subcutaneous adipose tissue (SAT) of obese patients, and higher adipose 11␤-HSD-1 was associated with features of the metabolic syndrome. To date, there is no evidence for an increased expression of 11␤-HSD-1 in human visceral adipose tissue (VAT), although VAT is the major predictor for insulin resistance and the metabolic syndrome. Research Methods and Procedures: 11␤-HSD-1 and hexose-6-phosphate dehydrogenase (the enzyme responsible for the synthesis of nicotinamide adenine dinucleotide phosphate, the cofactor required for 11␤-HSD-1 oxoreductase activity) mRNA levels were measured using real-time quantitative reverse transcriptase-polymerase chain reaction in abdominal SAT and VAT biopsies obtained from 10 normal-weight and 12 obese women. Adiponectin mRNA was used as an internal control.Results: 11␤-HSD-1 mRNA concentrations were significantly increased in both SAT and VAT of obese patients (720% and 450% of controls, respectively; p Ͻ 0.05) and correlated with hexose-6-phosphate dehydrogenase mRNA levels. The level of VAT 11␤-HSD-1 mRNA correlated with anthropometric parameters: BMI (r ϭ 0.41, p ϭ 0.05), waist circumference (r ϭ 0.44, p ϭ 0.04), abdominal sagittal diameter (r ϭ 0.51, p ϭ 0.02), and percentage fat (r ϭ 0.51, p ϭ 0.02). Discussion: Our results demonstrate for the first time that 11␤-HSD-1 mRNA expression is increased in VAT from obese patients. They strengthen the importance of 11␤-HSD-1 in human obesity and its associated complications and suggest the need of clinical studies with specific 11␤-HSD-1 inhibitors.

P16 and P14ARF are two tumor suppressors encoded by the locus ink4a-arf which is frequently deleted in human tumors. Recent experiments performed with mouse embryonic ®broblasts have shown that P14ARF is an upstream regulator of the P53 pathway. This raises the question as to whether in human tumors the loss of p14arf and mutation of p53 are mutually exclusive events which segregate with genetic alterations at other loci. To examine this question we performed a multigenic analysis on 29 gliomas. We analysed p53 and p14arf in relation with ®ve other genetic loci encoding the most frequently mutated genes in human gliomas: cdkn2a, mdm2, egfr, pten and the chromosomal regions 10q23.3 and 10q25-26. Our study shows for the ®rst time that p53 mutations and p14arf deletions appear mutually exclusive in human glioblastoma, suggesting that they may be functionally redundant in glioma tumorigenesis. The P53 pathway is, therefore, disrupted in 81.8% of malignant gliomas (WHO grades III and IV), either by mutation of the p53 gene (31.8%) or by p14arf deletion (54.5%). These tumors further showed MDM2 overexpression (9.1%), egfr oncogene ampli®cation/egfr overexpression (50%), pten mutations (27.3%) and loss of heterozygosity (LOH) at the chromosomal regions 10q23.3 (86.4%) and 10q25-26 (100%). These alterations did not segregate with p53 mutations or p14arf deletions, while p14arf and cdkn2a were always deleted. Oncogene (2000) 19, 3816 ± 3822.

After evaluation of 898 breast cancer patients, uPA mRNA expression emerged as a powerful prognostic indicator in ErbB2-positive tumors. These results were consistent among three independent study populations assayed by different techniques, including qrt-PCR and two microarray platforms.