Enhanced skin carcinogenesis and lack of thymus hyperplasia in transgenic mice expressing human cyclin D1b (CCND1b)

Autores
Rojas, Paola Andrea; Benavides, Fernando; Blando, Jorge; Pérez, Carlos; Cardenas, Kim; Richie, Ellen; Knudsen, Erik S.; Johnson, David G.; Senderowicz, Adrian M.; Rodriguez Puebla, Marcelo L.; Conti, Claudio
Año de publicación
2009
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Cyclin D1b is an alternative transcript of the cyclin D1 gene (CCND1) expressed in human tumors. Its abundance is regulated by a single base pair polymorphism at the exon 4/intron 4 boundary (nucleotide 870). Epidemiological studies have shown a correlation between the presence of the G870A allele (that favors the splicing for cyclin D1b) with increased risk and less favorable outcome in several forms of cancer. More recently, it has been shown that, unlike cyclin D1a, the alternative transcript D1b by itself has the capacity to transform fibroblasts in vitro. In order to study the oncogenic potential of cyclin D1b, we developed transgenic mice expressing human cyclin D1b under the control of the bovine K5 promoter (K5D1b mice). Seven founders were obtained and none of them presented any significant phenotype or developed spontaneous tumors. Interestingly, K5D1b mice do not develop the fatal thymic hyperplasia, which is characteristic of the cyclin D1a transgenic mice (K5D1a). Susceptibility to skin carcinogenesis was tested in K5D1b mice using two-stage carcinogenesis protocols. In two independent experiments, K5D1b mice developed higher papilloma multiplicity as compared with wild-type littermates. However, when K5D1b mice were crossed with cyclin D1KO mice, the expression of cyclin D1b was unable to rescue the carcinogenesis-resistant phenotype of the cyclin D1 KO mice. To further explore the role of cyclin D1b in mouse models of carcinogenesis we carried out in silico analysis and in vitro experiments to evaluate the existence of a mouse homologous of the human cyclin D1b transcript. We were unable to find any evidence of an alternatively spliced transcript in mouse Ccnd1. These results show that human cyclin D1b has different biological functions than cyclin D1a and confirm its oncogenic properties.
Fil: Rojas, Paola Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. University of Texas; Estados Unidos
Fil: Benavides, Fernando. University of Texas; Estados Unidos
Fil: Blando, Jorge. University of Texas; Estados Unidos
Fil: Pérez, Carlos. University of Texas; Estados Unidos
Fil: Cardenas, Kim. University of Texas; Estados Unidos
Fil: Richie, Ellen. University of Texas; Estados Unidos
Fil: Knudsen, Erik S.. Thomas Jefferson University; Estados Unidos
Fil: Johnson, David G.. University of Texas; Estados Unidos
Fil: Senderowicz, Adrian M.. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research; Estados Unidos
Fil: Rodriguez Puebla, Marcelo L.. University of North Carolina; Estados Unidos
Fil: Conti, Claudio. University of Texas; Estados Unidos
Materia
CYCLIN D1
SKIN CARCINOGENESIS
DMBA
TPA
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/25564

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repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Enhanced skin carcinogenesis and lack of thymus hyperplasia in transgenic mice expressing human cyclin D1b (CCND1b)Rojas, Paola AndreaBenavides, FernandoBlando, JorgePérez, CarlosCardenas, KimRichie, EllenKnudsen, Erik S.Johnson, David G.Senderowicz, Adrian M.Rodriguez Puebla, Marcelo L.Conti, ClaudioCYCLIN D1SKIN CARCINOGENESISDMBATPAhttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3Cyclin D1b is an alternative transcript of the cyclin D1 gene (CCND1) expressed in human tumors. Its abundance is regulated by a single base pair polymorphism at the exon 4/intron 4 boundary (nucleotide 870). Epidemiological studies have shown a correlation between the presence of the G870A allele (that favors the splicing for cyclin D1b) with increased risk and less favorable outcome in several forms of cancer. More recently, it has been shown that, unlike cyclin D1a, the alternative transcript D1b by itself has the capacity to transform fibroblasts in vitro. In order to study the oncogenic potential of cyclin D1b, we developed transgenic mice expressing human cyclin D1b under the control of the bovine K5 promoter (K5D1b mice). Seven founders were obtained and none of them presented any significant phenotype or developed spontaneous tumors. Interestingly, K5D1b mice do not develop the fatal thymic hyperplasia, which is characteristic of the cyclin D1a transgenic mice (K5D1a). Susceptibility to skin carcinogenesis was tested in K5D1b mice using two-stage carcinogenesis protocols. In two independent experiments, K5D1b mice developed higher papilloma multiplicity as compared with wild-type littermates. However, when K5D1b mice were crossed with cyclin D1KO mice, the expression of cyclin D1b was unable to rescue the carcinogenesis-resistant phenotype of the cyclin D1 KO mice. To further explore the role of cyclin D1b in mouse models of carcinogenesis we carried out in silico analysis and in vitro experiments to evaluate the existence of a mouse homologous of the human cyclin D1b transcript. We were unable to find any evidence of an alternatively spliced transcript in mouse Ccnd1. These results show that human cyclin D1b has different biological functions than cyclin D1a and confirm its oncogenic properties.Fil: Rojas, Paola Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. University of Texas; Estados UnidosFil: Benavides, Fernando. University of Texas; Estados UnidosFil: Blando, Jorge. University of Texas; Estados UnidosFil: Pérez, Carlos. University of Texas; Estados UnidosFil: Cardenas, Kim. University of Texas; Estados UnidosFil: Richie, Ellen. University of Texas; Estados UnidosFil: Knudsen, Erik S.. Thomas Jefferson University; Estados UnidosFil: Johnson, David G.. University of Texas; Estados UnidosFil: Senderowicz, Adrian M.. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research; Estados UnidosFil: Rodriguez Puebla, Marcelo L.. University of North Carolina; Estados UnidosFil: Conti, Claudio. University of Texas; Estados UnidosWiley2009-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/25564Rojas, Paola Andrea; Benavides, Fernando; Blando, Jorge; Pérez, Carlos; Cardenas, Kim; et al.; Enhanced skin carcinogenesis and lack of thymus hyperplasia in transgenic mice expressing human cyclin D1b (CCND1b); Wiley; Molecular Carcinogenesis.; 48; 6; 6-2009; 508-5160899-19871098-2744CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1002/mc.20489/abstractinfo:eu-repo/semantics/altIdentifier/doi/10.1002/mc.20489info:eu-repo/semantics/altIdentifier/purl/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2705965/info:eu-repo/semantics/altIdentifier/pmid/18942117info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:57:14Zoai:ri.conicet.gov.ar:11336/25564instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:57:14.433CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Enhanced skin carcinogenesis and lack of thymus hyperplasia in transgenic mice expressing human cyclin D1b (CCND1b)
title Enhanced skin carcinogenesis and lack of thymus hyperplasia in transgenic mice expressing human cyclin D1b (CCND1b)
spellingShingle Enhanced skin carcinogenesis and lack of thymus hyperplasia in transgenic mice expressing human cyclin D1b (CCND1b)
Rojas, Paola Andrea
CYCLIN D1
SKIN CARCINOGENESIS
DMBA
TPA
title_short Enhanced skin carcinogenesis and lack of thymus hyperplasia in transgenic mice expressing human cyclin D1b (CCND1b)
title_full Enhanced skin carcinogenesis and lack of thymus hyperplasia in transgenic mice expressing human cyclin D1b (CCND1b)
title_fullStr Enhanced skin carcinogenesis and lack of thymus hyperplasia in transgenic mice expressing human cyclin D1b (CCND1b)
title_full_unstemmed Enhanced skin carcinogenesis and lack of thymus hyperplasia in transgenic mice expressing human cyclin D1b (CCND1b)
title_sort Enhanced skin carcinogenesis and lack of thymus hyperplasia in transgenic mice expressing human cyclin D1b (CCND1b)
dc.creator.none.fl_str_mv Rojas, Paola Andrea
Benavides, Fernando
Blando, Jorge
Pérez, Carlos
Cardenas, Kim
Richie, Ellen
Knudsen, Erik S.
Johnson, David G.
Senderowicz, Adrian M.
Rodriguez Puebla, Marcelo L.
Conti, Claudio
author Rojas, Paola Andrea
author_facet Rojas, Paola Andrea
Benavides, Fernando
Blando, Jorge
Pérez, Carlos
Cardenas, Kim
Richie, Ellen
Knudsen, Erik S.
Johnson, David G.
Senderowicz, Adrian M.
Rodriguez Puebla, Marcelo L.
Conti, Claudio
author_role author
author2 Benavides, Fernando
Blando, Jorge
Pérez, Carlos
Cardenas, Kim
Richie, Ellen
Knudsen, Erik S.
Johnson, David G.
Senderowicz, Adrian M.
Rodriguez Puebla, Marcelo L.
Conti, Claudio
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv CYCLIN D1
SKIN CARCINOGENESIS
DMBA
TPA
topic CYCLIN D1
SKIN CARCINOGENESIS
DMBA
TPA
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Cyclin D1b is an alternative transcript of the cyclin D1 gene (CCND1) expressed in human tumors. Its abundance is regulated by a single base pair polymorphism at the exon 4/intron 4 boundary (nucleotide 870). Epidemiological studies have shown a correlation between the presence of the G870A allele (that favors the splicing for cyclin D1b) with increased risk and less favorable outcome in several forms of cancer. More recently, it has been shown that, unlike cyclin D1a, the alternative transcript D1b by itself has the capacity to transform fibroblasts in vitro. In order to study the oncogenic potential of cyclin D1b, we developed transgenic mice expressing human cyclin D1b under the control of the bovine K5 promoter (K5D1b mice). Seven founders were obtained and none of them presented any significant phenotype or developed spontaneous tumors. Interestingly, K5D1b mice do not develop the fatal thymic hyperplasia, which is characteristic of the cyclin D1a transgenic mice (K5D1a). Susceptibility to skin carcinogenesis was tested in K5D1b mice using two-stage carcinogenesis protocols. In two independent experiments, K5D1b mice developed higher papilloma multiplicity as compared with wild-type littermates. However, when K5D1b mice were crossed with cyclin D1KO mice, the expression of cyclin D1b was unable to rescue the carcinogenesis-resistant phenotype of the cyclin D1 KO mice. To further explore the role of cyclin D1b in mouse models of carcinogenesis we carried out in silico analysis and in vitro experiments to evaluate the existence of a mouse homologous of the human cyclin D1b transcript. We were unable to find any evidence of an alternatively spliced transcript in mouse Ccnd1. These results show that human cyclin D1b has different biological functions than cyclin D1a and confirm its oncogenic properties.
Fil: Rojas, Paola Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. University of Texas; Estados Unidos
Fil: Benavides, Fernando. University of Texas; Estados Unidos
Fil: Blando, Jorge. University of Texas; Estados Unidos
Fil: Pérez, Carlos. University of Texas; Estados Unidos
Fil: Cardenas, Kim. University of Texas; Estados Unidos
Fil: Richie, Ellen. University of Texas; Estados Unidos
Fil: Knudsen, Erik S.. Thomas Jefferson University; Estados Unidos
Fil: Johnson, David G.. University of Texas; Estados Unidos
Fil: Senderowicz, Adrian M.. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research; Estados Unidos
Fil: Rodriguez Puebla, Marcelo L.. University of North Carolina; Estados Unidos
Fil: Conti, Claudio. University of Texas; Estados Unidos
description Cyclin D1b is an alternative transcript of the cyclin D1 gene (CCND1) expressed in human tumors. Its abundance is regulated by a single base pair polymorphism at the exon 4/intron 4 boundary (nucleotide 870). Epidemiological studies have shown a correlation between the presence of the G870A allele (that favors the splicing for cyclin D1b) with increased risk and less favorable outcome in several forms of cancer. More recently, it has been shown that, unlike cyclin D1a, the alternative transcript D1b by itself has the capacity to transform fibroblasts in vitro. In order to study the oncogenic potential of cyclin D1b, we developed transgenic mice expressing human cyclin D1b under the control of the bovine K5 promoter (K5D1b mice). Seven founders were obtained and none of them presented any significant phenotype or developed spontaneous tumors. Interestingly, K5D1b mice do not develop the fatal thymic hyperplasia, which is characteristic of the cyclin D1a transgenic mice (K5D1a). Susceptibility to skin carcinogenesis was tested in K5D1b mice using two-stage carcinogenesis protocols. In two independent experiments, K5D1b mice developed higher papilloma multiplicity as compared with wild-type littermates. However, when K5D1b mice were crossed with cyclin D1KO mice, the expression of cyclin D1b was unable to rescue the carcinogenesis-resistant phenotype of the cyclin D1 KO mice. To further explore the role of cyclin D1b in mouse models of carcinogenesis we carried out in silico analysis and in vitro experiments to evaluate the existence of a mouse homologous of the human cyclin D1b transcript. We were unable to find any evidence of an alternatively spliced transcript in mouse Ccnd1. These results show that human cyclin D1b has different biological functions than cyclin D1a and confirm its oncogenic properties.
publishDate 2009
dc.date.none.fl_str_mv 2009-06
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/25564
Rojas, Paola Andrea; Benavides, Fernando; Blando, Jorge; Pérez, Carlos; Cardenas, Kim; et al.; Enhanced skin carcinogenesis and lack of thymus hyperplasia in transgenic mice expressing human cyclin D1b (CCND1b); Wiley; Molecular Carcinogenesis.; 48; 6; 6-2009; 508-516
0899-1987
1098-2744
CONICET Digital
CONICET
url http://hdl.handle.net/11336/25564
identifier_str_mv Rojas, Paola Andrea; Benavides, Fernando; Blando, Jorge; Pérez, Carlos; Cardenas, Kim; et al.; Enhanced skin carcinogenesis and lack of thymus hyperplasia in transgenic mice expressing human cyclin D1b (CCND1b); Wiley; Molecular Carcinogenesis.; 48; 6; 6-2009; 508-516
0899-1987
1098-2744
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1002/mc.20489/abstract
info:eu-repo/semantics/altIdentifier/doi/10.1002/mc.20489
info:eu-repo/semantics/altIdentifier/purl/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2705965/
info:eu-repo/semantics/altIdentifier/pmid/18942117
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
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repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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