Next, we analyzed the protein expression profile of Tgf-α and Hb-egf, to visualize if these signaling peptides were processed into membrane-bound proforms or soluble forms, which are both bioactive.30,31 The low molecular weight soluble form of Tgf-α initially increases at the hyperplastic stage of RT2 progression before disappearing in later stages, whereas the membrane-bound proform of Tgf-α capable of stimulating EGFR phosphorylation,32,33 proliferation,34 and transformation35 in adjacent cells increases significantly at the angiogenic and tumor stages (>15-fold) of RT2 (Fig. 3B). This evidence concerns the gene EGFR and neoplasm.