Abstract 1085: TGFBR2-dependent alterations of glycosylation in MSI colorectal cancer

Autor:	Hanno Glimm, Claudia R. Ball, Johannes Gebert, Juergen Kopitz, Jennifer Lee, Kai Schoenig
Rok vydání:	2012
Předmět:	Genetics Cancer Research Glycosylation Colorectal cancer Recombinase-mediated cassette exchange Cancer Microsatellite instability Transforming growth factor beta Biology medicine.disease Frameshift mutation chemistry.chemical_compound Exon Oncology chemistry Cancer research medicine biology.protein
Zdroj:	Cancer Research. 72:1085-1085
ISSN:	1538-7445 0008-5472
DOI:	10.1158/1538-7445.am2012-1085
Popis:	Aberrant glycosylation is a common feature of many malignancies including colorectal cancers. About 15% of colorectal cancers show the microsatellite instability (MSI) phenotype that is associated with a high frequency of biallelic frameshift mutations in the exon 3 coding mononucleotide microsatellite of the Transforming growth factor beta receptor 2 (TGFBR2) gene. If and how disruption of normal TGFBR2 signaling in these MSI colorectal cancer cells is linked to altered glycan pattern is largely unexplored. To address this issue we used the TGFBR2-deficient MSI colon carcinoma cell line HCT116 as a model system. Stable clones enabling doxycycline-inducible expression of wildtype TGFBR2 transgene were generated by recombinase-mediated cassette exchange (RMCE). In two independent clones dox-inducible expression of wildtype TGFBR2 protein and functional reconstitution of TGFBR2-mediated signal transduction as recognized by target gene regulation (SMAD7, SERPINE, c-myc) and Phospho-SMAD2 analysis was confirmed by Western blot and qRT-PCR analysis. Metabolic labeling experiments using the sialic acid precursor 3H-N-acetyl-mannosamine revealed a significant decline of 30% and hence newly synthesized sialoglycoproteins in TGFBR2 expressing cells. Therefore, our findings demonstrate that this model system can be used as a versatile tool to study TGFBR2-dependent effects. Furthermore, our data reveal a TGFBR2 gene-dependent aberrant glycosylation pattern in the MSI colon cell line HCT116. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1085. doi:1538-7445.AM2012-1085
Databáze:	OpenAIRE
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