These observations, coupled with the distinct and separable phenotypes observed in the Tgf-α and Hb-egf mutants, implicate two parallel Egfr intercellular signaling circuits in these PNET tumors: one circuit involves membrane-tethered Tgf-α that signals in autocrine/juxtacrine fashion to Egfr expressed as well on cancer cells, thereby enhancing cancer cell survival, while the second circuit involves Hb-egf expressed in multiple cell types, which signals to Egfr expressed on pericytes of the tumor vasculature. The gene discussed is EGFR; the disease is cancer.