Alternative definition : KEGG: Normal duct epithelium progresses to infiltrating cancer through a series of
histologically defined precursors (PanINs). The overexpression of HER-2/neu and activating
point mutations in the K-ras gene occur early, inactivation of the p16 gene at an
intermediate stage, and the inactivation of p53, SMAD4, and BRCA2 occur relatively
late. Activated K-ras engages multiple effector pathways. Although EGF receptors are
conventionally regarded as upstream activators of RAS proteins, they can also act
as RAS signal transducers via RAS-induced autocrine activation of the EGFR family
ligands. Pancreatic ductal adenocarcinoma (PDA) show elevated expression of EGF receptors
(e.g. HER2/neu) and their ligands (e.g. TGF-alpha) consistent with the presence of
this autocrine loop. Moreover, PDA shows extensive genomic instability and aneuploidy.
Telomere attrition and mutations in p53 and BRCA2 are likely to contribute to these
phenotypes. Inactivation of the SMAD4 tumour suppressor gene leads to loss of the
inhibitory influence of the transforming growth factor-beta signaling pathway.;
Automatic exact mappings (from CISMeF team)