Tumoral epithelial and stromal expression of SMAD proteins in pancreatic ductal adenocarcinomas

Journal of Hepato-biliary-pancreatic Sciences
Adriana Handra-LucaAnne Couvelard

Abstract

SMAD proteins, intracellular mediators of the transforming growth factor (TGF)-beta pathway, function within two axes, the SMAD1/5/8 and SMAD2/3, connected to TGF-beta and bone morphogenetic protein (BMP) ligands. The SMAD proteins of these two axes dimerize with SMAD4 and translocate to the nucleus. SMAD signaling is characterized by a dichotomic functioning, with tumor-suppressive functions and with loss of normal growth inhibitory responses, depending on the carcinogenesis stage. SMAD proteins also have pro-tumor effects including abnormal extracellular matrix production. Among tumors, pancreatic cancers harbor SMAD4 inactivation the most frequently and the SMAD proteins are considered to be key factors in pancreatic carcinogenesis. Our aims were to study the expression patterns of the different types of SMAD proteins in pancreatic ductal adenocarcinomas treated by surgical resection (without neoadjuvant treatment) and their correlations with morphological and clinical characteristics. We examined the immunohistochemical expression of SMAD4, SMAD1/5/8, and SMAD2/3 in 99 pancreatic ductal adenocarcinomas. Antibodies directed against the activated, phosphorylated forms of proteins were used when appropriate (SMAD1/5/8, SMAD2/3...Continue Reading

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Citations

Oct 31, 2013·Journal of Clinical Pathology·Adriana Handra-LucaAnne Couvelard
Mar 30, 2017·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Magdalena WitkowskaPiotr Smolewski
Nov 15, 2016·Molecular Medicine Reports·Dadong WangZhi-Wei Liu
Jun 1, 2014·Disease Models & Mechanisms·Marco SchiavoneFrancesco Argenton

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