GADD45A is responsible for identifying residues for DNA demethylation by DNA repair25, 41. We modulated GADD45A in pancreatic cancer cells using either siRNA to knockdown or adenoviral infection to overexpress GADD45A and examined the effects on AREG and EREG expression. As depicted in Fig. 4, knockdown of GADD45A (Fig. 5E) resulted in decreased expression of AREG and EREG regardless of integrin α6β4 expression (Fig. 5C,D). Similarly, overexpression of GADD45A (Fig. 5H) resulted in a further increase in AREG and EREG expression, only in Panc1-3D7 cells (Fig. 5F vs G). These data indicate that GADD45A is a required for and is potentially a rate-limiting step in gene activation of AREG and EREG downstream of integrin α6β4 signaling.