HES1 and hepatocellular carcinoma: As seen in Figure 4A, western blot analysis shows that Notch activation (ICN1 and ICN4) in HCC cells increased the expression of the Notch target gene HES1 and the nuclear receptor NR4A2 (Nurr1), but suppressed the expression of HDAC4 and tumor suppressors p21 and p63, indicating the involvement of NR4A2 and tumor suppressors in Notch-mediated signaling cascades.