Overexpression of the Growth arrest specific 1 (Gas1) gene reduces the in vivo progression of murine hepatocellular carcinoma and restores gene expression level. Mus musculus

Mice developing diethylnitrosamine (DEN)-induced hepatocellular carcinoma were transfected in vivo with Gas1 by hydrodynamic gene delivery. The treatment significantly (p < 0.05) reduced the number of large tumors (more than 2 mm diameter) and histological analyses revealed that the number of carcinoma foci in liver was reduced in favor of less malignant lesions, such as hyperplastic areas, and that the number of lung metastases was also diminished. To study the effects of DEN and the subsequent transfection with Gas1, an expression microarray experiment was designed in which the transcription of 20758 genes in liver was determined. A triangular analysis of microarray data shows that transfection with Gas1 restores the level of transcription level of 182 out of the 698 genes, whose expression was affected by DEN. Therefore, transfection of liver tumor-bearing animals with Gas1 significantly reduces the size and proliferative activity of tumors and restores the transcriptional profile of the liver. Overall design: Here we studied effects of diethylnitrosamine treatment of mice on the transcription of 20758 liver genes and the consequences of transfecting the livers with Gas1.