Wnt pathway-related gene expression during malignant progression in ulcerative colitis
Autor: | Riccardo Fodde, Patrick Franken, Ernst J. Kuipers, Herman van Dekken, Kees J. Vissers, W. Ruud Schouten, Josiane C. Wink, Wim C. J. Hop, C. Janneke van der Woude |
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Přispěvatelé: | Pathology, Surgery, Epidemiology, Gastroenterology & Hepatology |
Rok vydání: | 2007 |
Předmět: |
Adult
Male Histology Biology medicine.disease_cause Cyclin D1 Downregulation and upregulation medicine Humans Aged Aged 80 and over Oncogene Wnt signaling pathway Cell Biology General Medicine Middle Aged medicine.disease Immunohistochemistry Gene Expression Regulation Neoplastic Wnt Proteins Cell Transformation Neoplastic Dysplasia Catenin Colonic Neoplasms Disease Progression Cancer research Adenocarcinoma Colitis Ulcerative Female Carcinogenesis Signal Transduction |
Zdroj: | Acta Histochemica, 109(4), 266-272. Urban und Fischer Verlag Jena |
ISSN: | 1618-0372 0065-1281 |
Popis: | Summary Long-standing ulcerative colitis (UC) has been associated with a high risk of developing colonic adenocarcinoma. Importantly, both low- and high-grade dysplasia are strongly related to the presence or development of malignancy. The canonical Wnt/ β -catenin signaling pathway is of crucial importance in cancer development and progression, but its role in UC-related carcinogenesis remains to be determined. We evaluated the immunolabeling patterns of β -catenin, as well as the products of Wnt-associated cancer genes E-cadherin, cyclin D1 and c-myc, along the dysplasia–carcinoma pathway in UC. For this purpose, immunohistochemistry (IHC) was performed on 18 adenocarcinomas and 17 dysplasias, derived from 21 patients. We found that intracellular β -catenin accumulation, the hallmark of Wnt signaling activation, is observed in dysplasia, together with enhanced labeling of nuclear protein cyclin D1 and reduction of membranous labeling of E-cadherin. c-myc displayed moderate immunolabeling in the (pre)malignant lesions. Thus, the Wnt pathway is activated in early stages of malignant progression in UC. Furthermore, upregulation of the oncogene cyclin D1 and downregulation of tumor suppressor E-cadherin also occurs in the (pre)neoplastic state. This may contribute to the high potential for malignant degeneration of dysplasia in UC-related colitis. |
Databáze: | OpenAIRE |
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