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Increased tumorigenesis associated with loss of the tumor suppressor gene Cadm1

BACKGROUND: CADM1 encodes an immunoglobulin superfamily (IGSF) cell adhesion molecule. Inactivation of CADM1, either by promoter hypermethylation or loss of heterozygosity, has been reported in a wide variety of tumor types, thus it has been postulated as a tumor suppressor gene. FINDINGS: We show f...

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Autores principales: van der Weyden, Louise, Arends, Mark J, Rust, Alistair G, Poulogiannis, George, McIntyre, Rebecca E, Adams, David J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3489691/
https://www.ncbi.nlm.nih.gov/pubmed/22553910
http://dx.doi.org/10.1186/1476-4598-11-29
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author van der Weyden, Louise
Arends, Mark J
Rust, Alistair G
Poulogiannis, George
McIntyre, Rebecca E
Adams, David J
author_facet van der Weyden, Louise
Arends, Mark J
Rust, Alistair G
Poulogiannis, George
McIntyre, Rebecca E
Adams, David J
author_sort van der Weyden, Louise
collection PubMed
description BACKGROUND: CADM1 encodes an immunoglobulin superfamily (IGSF) cell adhesion molecule. Inactivation of CADM1, either by promoter hypermethylation or loss of heterozygosity, has been reported in a wide variety of tumor types, thus it has been postulated as a tumor suppressor gene. FINDINGS: We show for the first time that Cadm1 homozygous null mice die significantly faster than wildtype controls due to the spontaneous development of tumors at an earlier age and an increased tumor incidence of predominantly lymphomas, but also some solid tumors. Tumorigenesis was accelerated after irradiation of Cadm1 mice, with the reduced latency in tumor formation suggesting there are genes that collaborate with loss of Cadm1 in tumorigenesis. To identify these co-operating genetic events, we performed a Sleeping Beauty transposon-mediated insertional mutagenesis screen in Cadm1 mice, and identified several common insertion sites (CIS) found specifically on a Cadm1-null background (and not wildtype background). CONCLUSION: We confirm that Cadm1 is indeed a bona fide tumor suppressor gene and provide new insights into genetic partners that co-operate in tumorigenesis when Cadm1-expression is lost.
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spelling pubmed-34896912012-11-06 Increased tumorigenesis associated with loss of the tumor suppressor gene Cadm1 van der Weyden, Louise Arends, Mark J Rust, Alistair G Poulogiannis, George McIntyre, Rebecca E Adams, David J Mol Cancer Short Communication BACKGROUND: CADM1 encodes an immunoglobulin superfamily (IGSF) cell adhesion molecule. Inactivation of CADM1, either by promoter hypermethylation or loss of heterozygosity, has been reported in a wide variety of tumor types, thus it has been postulated as a tumor suppressor gene. FINDINGS: We show for the first time that Cadm1 homozygous null mice die significantly faster than wildtype controls due to the spontaneous development of tumors at an earlier age and an increased tumor incidence of predominantly lymphomas, but also some solid tumors. Tumorigenesis was accelerated after irradiation of Cadm1 mice, with the reduced latency in tumor formation suggesting there are genes that collaborate with loss of Cadm1 in tumorigenesis. To identify these co-operating genetic events, we performed a Sleeping Beauty transposon-mediated insertional mutagenesis screen in Cadm1 mice, and identified several common insertion sites (CIS) found specifically on a Cadm1-null background (and not wildtype background). CONCLUSION: We confirm that Cadm1 is indeed a bona fide tumor suppressor gene and provide new insights into genetic partners that co-operate in tumorigenesis when Cadm1-expression is lost. BioMed Central 2012-05-03 /pmc/articles/PMC3489691/ /pubmed/22553910 http://dx.doi.org/10.1186/1476-4598-11-29 Text en Copyright ©2012 van der Weyden et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Short Communication
van der Weyden, Louise
Arends, Mark J
Rust, Alistair G
Poulogiannis, George
McIntyre, Rebecca E
Adams, David J
Increased tumorigenesis associated with loss of the tumor suppressor gene Cadm1
title Increased tumorigenesis associated with loss of the tumor suppressor gene Cadm1
title_full Increased tumorigenesis associated with loss of the tumor suppressor gene Cadm1
title_fullStr Increased tumorigenesis associated with loss of the tumor suppressor gene Cadm1
title_full_unstemmed Increased tumorigenesis associated with loss of the tumor suppressor gene Cadm1
title_short Increased tumorigenesis associated with loss of the tumor suppressor gene Cadm1
title_sort increased tumorigenesis associated with loss of the tumor suppressor gene cadm1
topic Short Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3489691/
https://www.ncbi.nlm.nih.gov/pubmed/22553910
http://dx.doi.org/10.1186/1476-4598-11-29
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