title: Growth Arrest Specific 1 (Gas1) Gene Overexpression in Liver Reduces the In Vivo Progression of Murine Hepatocellular Carcinoma and Partially Restores Gene Expression Levels.
abstract: The prognosis of hepatocellular carcinoma patients is usually poor, the size of tumors being a limiting factor for surgical treatments. Present results suggest that the overexpression of Gas1 (growth arrest specific 1) gene reduces the size, proliferating activity and malignancy of liver tumors. Mice developing diethylnitrosamine-induced hepatocellular carcinoma were subjected to hydrodynamic gene delivery to overexpress Gas1 in liver. This treatment significantly (p < 0.05) reduced the number of large tumors, while the difference in the total number of lesions was not significant. Moreover, the number of carcinoma foci in the liver and the number of lung metastases were reduced. These results are related with the finding that overexpression of Gas1 in Hepa 1-6 cells arrests cell cycle before S phase, with a significant (p < 0.01) and concomitant reduction in the expression of cyclin E2 gene. In addition, a triangular analysis of microarray data shows that Gas1 overexpression restores the transcription levels of 150 genes whose expression was affected in the diethylnitrosamine-induced tumors, thirteen of which are involved in the hedgehog signaling pathway. Since the in vivo Gas1 gene delivery to livers of mice carrying hepatocellular carcinoma reduces the size and proliferating activity of tumors, partially restoring the transcriptional profile of the liver, the present study opens promising insights towards a therapeutic approach for hepatocellular carcinoma.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Valencia, Burjassot, Valencia, Spain.
authors.forename: Natalia
authors.initials: N
authors.lastname: Sacilotto
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Valencia, Burjassot, Valencia, Spain; Institute of Health Research INCLIVA, Valencia, Spain.
authors.forename: Josefa
authors.initials: J
authors.lastname: Castillo
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Valencia, Burjassot, Valencia, Spain; Institute of Health Research INCLIVA, Valencia, Spain.
authors.forename: Ángela L
authors.initials: ÁL
authors.lastname: Riffo-Campos
authors.affiliation: Department of Medicine and Animal Surgery, University Complutense, Madrid, Spain.
authors.forename: Juana M
authors.initials: JM
authors.lastname: Flores
authors.affiliation: Department of Physiology, Anatomy and Genetics, Oxford University, Oxford, United Kingdom.
authors.forename: Olivia
authors.initials: O
authors.lastname: Hibbitt
authors.affiliation: Department of Physiology, Anatomy and Genetics, Oxford University, Oxford, United Kingdom.
authors.forename: Richard
authors.initials: R
authors.lastname: Wade-Martins
authors.affiliation: Department of Cell Biology, University of Valencia, Burjassot, Valencia, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: López
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Valencia, Burjassot, Valencia, Spain; Institute of Health Research INCLIVA, Valencia, Spain.
authors.forename: M Isabel
authors.initials: MI
authors.lastname: Rodrigo
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Valencia, Burjassot, Valencia, Spain; Institute of Health Research INCLIVA, Valencia, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Franco
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Valencia, Burjassot, Valencia, Spain.
authors.forename: Gerardo
authors.initials: G
authors.lastname: López-Rodas
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018450:Disease Progression; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D057446:Hydrodynamics; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D060888:Real-Time Polymerase Chain Reaction; D014162:Transfection
chemical_list: D018797:Cell Cycle Proteins; D058851:GPI-Linked Proteins; C501180:Gas1 protein, mouse