Growth Arrest Specific 1 (Gas1) Gene Overexpression in Liver Reduces the In Vivo Progression of Murine Hepatocellular Carcinoma and Partially Restores Gene Expression Levels
| Autor: | Richard Wade-Martins, Josefa Castillo, Natalia Sacilotto, Angela L. Riffo-Campos, M. Isabel Rodrigo, Olivia Hibbitt, Carlos Alberto Matheus López, Gerardo López-Rodas, Luis Franco, Juana M. Flores |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Male
Carcinoma Hepatocellular lcsh:Medicine Cell Cycle Proteins Gene delivery Biology GPI-Linked Proteins Real-Time Polymerase Chain Reaction Transfection Mice Cell Line Tumor Gene expression Carcinoma medicine Animals lcsh:Science Lung Cell Proliferation Regulation of gene expression Multidisciplinary Microarray analysis techniques Liver Neoplasms lcsh:R Cell cycle medicine.disease Molecular biology Hedgehog signaling pathway Gene Expression Regulation Neoplastic Liver Hepatocellular carcinoma Disease Progression Hydrodynamics lcsh:Q Research Article |
| Zdroj: | PLoS ONE, Vol 10, Iss 7, p e0132477 (2015) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|