Increased phospholipase C (PL-C) activity is associated with cellular growth and division; over expression of Gqa or transfection of cells with constituitively activated forms can potentiate cellular transformation. We hypothesized that alterations in Gq linked to PL-C transmembrane signal transduction pathways may regulate growth of HCC. Tumorigenic H4IIH hepatoma cells ( 10°) previously grown to 80-85% confluence in culture were inoculated into the right hepatic lobe of male AC1 rats with reproducible parenchymal tumor growths (10-15mm diameter) occuring 12-14 days post inoculation. Membranes were prepared from right (tumor bearing) and left (control) hepatic lobes. Gqa/G, expression was determined by Western blot analysis while functional activity was determined by inositol trisphosphate ( IP,) formation in acid extracts prepared from each lobe. Gqa/GH expression was significantly increased in HCC as compared to control. Gqa/GM expression in normal ACI rats (not previously inoculated with H4IIE) was not significantly different from control lobes of tumor bearing animals. Functional studies demonstrated IP, levels in tumor bearing rats versus normal rats were increased 2-3 fold. This data suggests that HCC is associated with elevated Gqa/GM expression and increased IP, formation. This may reflect cellular rnitogenesis through a PI.-C dependent pathway in H4IIE hepatoma cells.
|Original language||English (US)|
|State||Published - Dec 1 1996|
ASJC Scopus subject areas
- Molecular Biology