Fig. 4

EGF and HBEGF induced AREG expression and actuated MAPK and PI3K/Akt pathways in OSCC cell lines. a Both EGF and HBEGF stimulated AREG mRNA expression after two h, peaked at four h and disappeared after 24 h (left panel, Student’s t-test, ***p < 0.001). This was accompanied by increased AREG protein concentration in the supernatant during the following 48 h (right panel; untreated cells were used as control group; Student’s t-test, ***p < 0.001). A representative experiments in the D2 cell line is shown. b EGF induced phosphorylation of the EGF receptor, ERK, p38, JNK, Akt and ErbB2 could be completely inhibited by specific kinase inhibitors. Western blotting from a representative experiment using the D2 cell line