Tensin4 (TNS4) is upregulated by Wnt signalling in adenomas in multiple intestinal neoplasia (Min) mice

Autor:	Abdolrahman S. Nateri, Mohammad Ilyas, Abdulaziz Alfahed, Teresa P Raposo
Rok vydání:	2020
Předmět:	Genes APC Adenoma Colorectal cancer Motility Mice Transgenic Biology multiple intestinal neoplasia medicine.disease_cause HCT116 Pathology and Forensic Medicine Apc Min/+ Adenomatous Polyps Downregulation and upregulation Tensins Intestinal Neoplasms Intestine Small medicine Animals Humans Wnt Signaling Pathway Molecular Biology beta Catenin Wnt signalling Oncogene Original Articles Cell Biology HCT116 Cells medicine.disease digestive system diseases Up-Regulation Gene Expression Regulation Neoplastic Mice Inbred C57BL Blot Disease Models Animal Cancer research Immunohistochemistry Female Original Article KRAS TNS4
Zdroj:	International Journal of Experimental Pathology
ISSN:	1365-2613 0959-9673
DOI:	10.1111/iep.12352
Popis:	Summary Apc Min/+ mice are regarded as a standard animal model of colorectal cancer (CRC). Tensin4 (TNS4 or Cten) is a putative oncogene conferring features of stemness and promoting motility. Our objective was to assess TNS4 expression in intestinal adenomas and determine whether TNS4 is upregulated by Wnt signalling. ApcMin/+ mice (n = 11) were sacrificed at approximately 120 days old at the onset of anaemia signs. Small intestines were harvested, and Swiss roll preparations were tested for TNS4 expression by immunohistochemistry (IHC). Individual polyps were also separately collected (n = 14) and tested for TNS4 mRNA expression and Kras mutation. The relationship between Wnt signalling and TNS4 expression was tested by Western blotting in the human CRC cell line HCT116 after inhibition of β‐catenin activity with MSAB or its increase by transfection with a Flag β‐catenin expression vector. Overall, 135/148 (91.2%) of the total intestinal polyps were positive for TNS4 expression by IHC, whilst adjacent normal areas were negative. RT‐qPCR analysis showed approximately 5‐fold upregulation of TNS4 mRNA in the polyps compared to adjacent normal tissue and no Kras mutations were detected. In HCT116, β‐catenin inhibition resulted in reduced TNS4 expression, and conversely, β‐catenin overexpression resulted in increased TNS4 expression. In conclusion, this is the first report linking aberrant Wnt signalling to upregulation of TNS4 both during initiation of intestinal adenomas in mice and in in vitro models. The exact contribution of TNS4 to adenoma development remains to be investigated, but the Apc Min/+ mouse represents a good model to study this.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::80303cc75ddd061e5552d78853470fbe https://doi.org/10.1111/iep.12352 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
Nepřihlášeným uživatelům se plný text nezobrazuje	K zobrazení výsledku je třeba se přihlásit.