AREG and liver cancer: Furthermore, ADAM17/TACE is induced by treatment with estradiol (E2) of liver cancer cells (Figure 4), indicating that estrogen may increase AREG activity in the malignant liver either directly (through the upregulation of the AREG gene, increase of its transcriptional activity or protein biosynthesis) or indirectly (via the induction of ADAM17/TACE enzyme) or both [52].