title: Forced expression of RDH10 gene retards growth of HepG2 cells.
abstract: The constitutive over-expression of the retinol dehydrogenase 10 (RDH10) gene, involved in retinoic acid (RA) biosynthesis, produced in HepG2 cells a significant antiproliferative response, but not signs of apoptosis. An indirect assay based on the Chloramphenicol AcetylTransferase (CAT) reporter gene driven by a retinoic acid responsive element (RARE) suggests in genetically modified HepG2 cells an increase of the endogenous RA concentration. Furthermore, the growth arrest of HepG2 cells over-expressing the RDH10 gene was associated with the upregulation and downregulation of, respectively, RARbeta/p21(Cip1) and CycE/CdK2 mRNAs. These results indicated that forced expression of RDH10 produces antiproliferative effects highly comparable to those achieved by retinoids treatment and thus the development of a gene therapy, finalized at the restoration of the enzymatic and receptorial machinery of the RA pathway, could be a possible curative strategy for hepatocellular carcinoma (HCC).
authors.affiliation: Department of Biology and Genetics for Medical Sciences, University of Milan, Via Viotti 3/5, Milan 20133, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Rossi
authors.forename: Paola
authors.initials: P
authors.lastname: Picozzi
authors.forename: Beatrice
authors.initials: B
authors.lastname: Bodega
authors.forename: Cistiana
authors.initials: C
authors.lastname: Lavazza
authors.forename: Carmelo
authors.initials: C
authors.lastname: Carlo-Stella
authors.forename: Anna
authors.initials: A
authors.lastname: Marozzi
authors.forename: Enrico
authors.initials: E
authors.lastname: Ginelli
mesh_terms: D000429:Alcohol Oxidoreductases / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D002453:Cell Cycle / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics*; D014212:Tretinoin / Q000378:metabolism*
chemical_list: D014212:Tretinoin; D000429:Alcohol Oxidoreductases; C113992:trans-retinol dehydrogenase