High expression of the evolutionarily conserved alpha/beta hydrolase domain containing 6 (ABHD6) in Ewing tumors.
Despite improvements in the treatment of patients with Ewing family tumors (EFT), the prognosis for patients with advanced disease is still unsatisfactory. Recently, we identified lipase I as an EFT-associated gene that might be interesting for the development of new immunological or pharmacological treatment strategies. Lipase I is a member of the large protein superfamilies of alpha/beta hydrolases and serine hydrolases. In the present paper we describe high expression of another member of these superfamilies in EFT. By DNA microarray data base mining we found exceptional high expression of alpha/beta hydrolase domain containing 6 (ABHD6) in EFT but not in other sarcomas. Expression of ABHD6 in EFT correlated with expression of another EFT-associated gene, aristaless. Analysis of ABHD6-associated GGAA microsatellites revealed shorter microsatellites in EFT with lack of ABHD6 expression. ABHD6 homologues were found in varying chordata but not in other animal species. Based on homology modeling we predicted the 3D-structure of ABHD6, which shows high similarity with bacterial homoserine transacetylases. High expression of ABHD6 in EFT in comparison to normal tissues and other tumors suggests that ABHD6 might be an interesting new diagnostic or therapeutic target for EFT. However, knock down of ABHD6 in EFT cells did not inhibit tumor cell growth.
Children's Cancer Research Center, Martin-Luther-University Halle-Wittenberg, University Clinic and Polyclinic for Child and Adolescent Medicine, Halle, Germany.
Daniela
D
Max
Manuela
M
Hesse
Ines
I
Volkmer
Martin S
MS
Staege
D001859:Bone Neoplasms; D002265:Carboxylic Ester Hydrolases / Q000235:genetics; D045744:Cell Line, Tumor; D019143:Evolution, Molecular; D006801:Humans; D008049:Lipase / Q000235:genetics; D008994:Monoacylglycerol Lipases / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D011379:Prognosis; D012512:Sarcoma, Ewing / Q000201:enzymology* / Q000401:mortality
D002265:Carboxylic Ester Hydrolases; C474609:CES1 protein, human; C540878:ABHD6 protein, human; D008994:Monoacylglycerol Lipases; D008049:Lipase