The hypothesis of an intracellular (cytoplasmatic) generation of ANGII (Fig. 5, Model A) is supported by the fact that (1) the effect of intracellular dialysis of renin is potentiated by concomitant application of angiotensinogen20, and, (2) that artificial overexpression of a mutated non-secretory angiotensinogen in the cytosol in hepatoma cells increased mitogenic activity dependent on renin as well as AT1R functions33. The gene discussed is REN; the disease is hepatocellular carcinoma.