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This study was performed to gain a better understanding of the abnormal signaling that occurs in PDAC compared with normal duct epithelia.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>We performed immunohistochemistry on a tissue microarray of 26 PDAC, 13 normal appearing adjacent pancreatic ductal epithelia, and 12 normal non-PDAC ducts. We compared the levels of 18 signaling proteins including growth factor receptors, tumor suppressors and 13 of their putative downstream phosphorylated (p-) signal transducers in PDAC to those in normal ductal epithelia.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>The overall profiles of signaling protein expression levels, activation states and sub-cellular distribution in PDAC cells were distinguishable from non-neoplastic ductal epithelia. The ERK pathway activation was correlated with high levels of <jats:sup>S2448<\/jats:sup>p-mTOR (100%, p = 0.05), <jats:sup>T389<\/jats:sup>p-S6K (100%, p = 0.02 and <jats:sup>S235\/236<\/jats:sup>p-S6 (86%, p = 0.005). Additionally, <jats:sup>T389<\/jats:sup>p-S6K correlated with <jats:sup>S727<\/jats:sup>p-STAT3 (86%, p = 0.005). Advanced tumors with lymph node metastasis were characterized by high levels of <jats:sup>S276<\/jats:sup>p-NF\u03baB (100%, p = 0.05) and <jats:sup>S9<\/jats:sup>p-GSK3\u03b2 (100%, p = 0.05). High levels of PKB\u03b2\/AKT2, EGFR, as well as nuclear <jats:sup>T202\/Y204<\/jats:sup>p-ERK and <jats:sup>T180\/Y182<\/jats:sup>p-p38 were observed in normal ducts adjacent to PDAC compared with non-cancerous pancreas.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>Multiple signaling proteins are activated in pancreatic duct cell carcinogenesis including those associated with the ERK, PKB\/AKT, mTOR and STAT3 pathways. The ERK pathway activation appears also increased in duct epithelia adjacent to carcinoma, suggesting tumor micro-environmental effects.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1471-2407-8-43","type":"journal-article","created":{"date-parts":[[2008,2,7]],"date-time":"2008-02-07T07:13:30Z","timestamp":1202368410000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Immunohistochemical analysis of changes in signaling pathway activation downstream of growth factor receptors in pancreatic duct cell carcinogenesis"],"prefix":"10.1186","volume":"8","author":[{"given":"Nhu-An","family":"Pham","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joerg","family":"Schwock","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vladimir","family":"Iakovlev","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Greg","family":"Pond","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David W","family":"Hedley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming-Sound","family":"Tsao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2008,2,6]]},"reference":[{"issue":"15","key":"981_CR1","doi-asserted-by":"publisher","first-page":"2213","DOI":"10.1016\/j.ejca.2005.04.044","volume":"41","author":"G Garcea","year":"2005","unstructured":"Garcea G, Neal CP, Pattenden CJ, Steward WP, Berry DP: Molecular prognostic markers in pancreatic cancer: a systematic review. 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