CONTEXT: Childhood adrenocortical tumors (ACTs) have a fetal adrenal phenotype and overexpress steroidogenic factor-1 (SF-1). Nephroblastoma overexpressed (NOV)/cysteine-rich protein 61/connective tissue growth factor/nephroblastoma overexpressed gene-3 mRNA is significantly down-regulated in childhood ACTs. OBJECTIVE: The objective of the study was to measure NOV protein levels in childhood ACTs and characterize NOV expression regulation and biological function in human adrenocortical cells. DESIGN AND SETTING: Protein extracts from ACT and normal adrenal cortex samples, human adrenocortical carcinoma H295R, primary adrenocortical tumors and fetal adrenal cultures, tissue culture supernatants, and cell lysates from H295R cells overexpressing SF-1 in an inducible fashion were used. MAIN OUTCOME MEASURES: NOV protein levels were measured by enzyme-linked immunoassay and immunoblot. Transient transfection assays were used to study the activity of NOV promoter. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling, caspase assays, and flow cytometry were used to assess the proapoptotic activity of NOV on cells in culture. RESULTS: NOV mRNA and protein expression is lower in childhood ACTs than in normal adrenal cortex. No significant difference was observed between adenomas and carcinomas. SF-1 overexpression down-regulates NOV at the transcriptional level. NOV has a selective proapoptotic activity toward human adrenocortical cells. The C-terminal domain of NOV is responsible for its proapoptotic effect. NOV protein is expressed in DAX-1-positive human fetal adrenal cells. CONCLUSIONS: NOV is a selective proapoptotic factor for human adrenocortical cells. Reduced expression of NOV in ACTs may play an important role in the process of childhood ACT tumorigenesis, accounting at least in part for the defect of apoptotic regression of the fetal adrenal that has been proposed to be responsible for tumor formation.
CONTEXT: Childhood adrenocortical tumors (ACTs) have a fetal adrenal phenotype and overexpress steroidogenic factor-1 (SF-1). Nephroblastoma overexpressed (NOV)/cysteine-rich protein 61/connective tissue growth factor/nephroblastoma overexpressed gene-3 mRNA is significantly down-regulated in childhood ACTs. OBJECTIVE: The objective of the study was to measure NOV protein levels in childhood ACTs and characterize NOV expression regulation and biological function in humanadrenocortical cells. DESIGN AND SETTING: Protein extracts from ACT and normal adrenal cortex samples, humanadrenocortical carcinoma H295R, primary adrenocortical tumors and fetal adrenal cultures, tissue culture supernatants, and cell lysates from H295R cells overexpressing SF-1 in an inducible fashion were used. MAIN OUTCOME MEASURES: NOV protein levels were measured by enzyme-linked immunoassay and immunoblot. Transient transfection assays were used to study the activity of NOV promoter. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling, caspase assays, and flow cytometry were used to assess the proapoptotic activity of NOV on cells in culture. RESULTS:NOV mRNA and protein expression is lower in childhood ACTs than in normal adrenal cortex. No significant difference was observed between adenomas and carcinomas. SF-1 overexpression down-regulates NOV at the transcriptional level. NOV has a selective proapoptotic activity toward humanadrenocortical cells. The C-terminal domain of NOV is responsible for its proapoptotic effect. NOV protein is expressed in DAX-1-positive human fetal adrenal cells. CONCLUSIONS:NOV is a selective proapoptotic factor for humanadrenocortical cells. Reduced expression of NOV in ACTs may play an important role in the process of childhood ACT tumorigenesis, accounting at least in part for the defect of apoptotic regression of the fetal adrenal that has been proposed to be responsible for tumor formation.
Authors: Joanne H Heaton; Michelle A Wood; Alex C Kim; Lorena O Lima; Ferdous M Barlaskar; Madson Q Almeida; Maria C B V Fragoso; Rork Kuick; Antonio M Lerario; Derek P Simon; Ibere C Soares; Elisabeth Starnes; Dafydd G Thomas; Ana C Latronico; Thomas J Giordano; Gary D Hammer Journal: Am J Pathol Date: 2012-07-15 Impact factor: 4.307
Authors: Mabrouka Doghman; Abeer El Wakil; Bruno Cardinaud; Emilie Thomas; Jinling Wang; Wei Zhao; Maria Helena C Peralta-Del Valle; Bonald C Figueiredo; Gerard P Zambetti; Enzo Lalli Journal: Cancer Res Date: 2010-05-18 Impact factor: 12.701
Authors: Zhiyong Lin; Viswanath Natesan; Hong Shi; Anne Hamik; Daiji Kawanami; Caili Hao; Ganapati H Mahabaleshwar; Weiye Wang; Zheng-Gen Jin; G Brandon Atkins; Sue M Firth; Laure Rittié; Bernard Perbal; Mukesh K Jain Journal: J Cell Commun Signal Date: 2010-08-11 Impact factor: 5.782
Authors: Sharon J Pitteri; Lellean JeBailey; Vitor M Faça; Jason D Thorpe; Melissa A Silva; Reneé C Ireton; Marc B Horton; Hong Wang; Liese C Pruitt; Qing Zhang; Kuang H Cheng; Nicole Urban; Samir M Hanash; Daniela M Dinulescu Journal: PLoS One Date: 2009-11-19 Impact factor: 3.240