Tissue Inhibitor of Metalloproteinase 1 Expression Associated with Gene Demethylation Confers Anoikis Resistance in Early Phases of Melanocyte Malignant Transformation
Autor(a) principal: | |
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Data de Publicação: | 2009 |
Outros Autores: | , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | http://repositorio.unifesp.br/handle/11600/31968 http://dx.doi.org/10.1593/tlo.09220 |
Resumo: | Although anoikis resistance has been considered a hallmark of malignant phenotype, the causal relation between neoplastic transformation and anchorage-independent growth remains undefined. We developed an experimental model of murine melanocyte malignant transformation, where a melanocyte lineage (melan-a) was submitted to sequential cycles of anchorage blockade, resulting in progressive morphologic alterations, and malignant transformation. Throughout this process, cells corresponding to premalignant melanocytes and melanoma cell lines were established and show progressive anoikis resistance and increased expression of Timp1. in melan-a melanocytes, Timp1 expression is suppressed by DNA methylation as indicated by its reexpression after 5-aza-2'-deoxycytidine treatment. Methylation-sensitive single-nucleotide primer extension analysis showed increased demethylation in Timp1 in parallel with its expression along malignant transformation. Interestingly, TIMP1 expression has already been related with negative prognosis in some human cancers. Although described as aMMP inhibitor, this protein has been associated with apoptosis resistance in different cell types. Melan-a cells overexpressing Timp1 showed increased survival in suspension but were unable to form tumors in vivo, whereas Timp1-overexpressing melanoma cells showed reduced latency time for tumor appearance and increased metastatic potential. Here, we demonstrated for the first time an increment in Timp1 expression since the early phases of melanocyte malignant transformation, associated to a progressive gene demethylation, which confers anoikis resistance. in this way, Timp1 might be considered as a valued marker for melanocyte malignant transformation. |
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Ricca, Tatiana Iervolino [UNIFESP]Liang, GangningSuenaga, Ana Paula Mitsue [UNIFESP]Han, Sang Won [UNIFESP]Jones, Peter A.Jasiulionis, Miriam Galvonas [UNIFESP]Universidade Federal de São Paulo (UNIFESP)Univ So Calif2016-01-24T13:58:56Z2016-01-24T13:58:56Z2009-12-01Translational Oncology. Ann Arbor: Neoplasia Press, v. 2, n. 4, p. 329-340, 2009.1936-5233http://repositorio.unifesp.br/handle/11600/31968http://dx.doi.org/10.1593/tlo.0922010.1593/tlo.09220WOS:000272551800018Although anoikis resistance has been considered a hallmark of malignant phenotype, the causal relation between neoplastic transformation and anchorage-independent growth remains undefined. We developed an experimental model of murine melanocyte malignant transformation, where a melanocyte lineage (melan-a) was submitted to sequential cycles of anchorage blockade, resulting in progressive morphologic alterations, and malignant transformation. Throughout this process, cells corresponding to premalignant melanocytes and melanoma cell lines were established and show progressive anoikis resistance and increased expression of Timp1. in melan-a melanocytes, Timp1 expression is suppressed by DNA methylation as indicated by its reexpression after 5-aza-2'-deoxycytidine treatment. Methylation-sensitive single-nucleotide primer extension analysis showed increased demethylation in Timp1 in parallel with its expression along malignant transformation. Interestingly, TIMP1 expression has already been related with negative prognosis in some human cancers. Although described as aMMP inhibitor, this protein has been associated with apoptosis resistance in different cell types. Melan-a cells overexpressing Timp1 showed increased survival in suspension but were unable to form tumors in vivo, whereas Timp1-overexpressing melanoma cells showed reduced latency time for tumor appearance and increased metastatic potential. Here, we demonstrated for the first time an increment in Timp1 expression since the early phases of melanocyte malignant transformation, associated to a progressive gene demethylation, which confers anoikis resistance. in this way, Timp1 might be considered as a valued marker for melanocyte malignant transformation.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo, Dept Microbiol Immunol & Parasitol, BR-04023900 São Paulo, BrazilUniv So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USAUniversidade Federal de São Paulo, Dept Biochem, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Ctr Interdisciplinar Terapia Genica, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Pharmacol, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Microbiol Immunol & Parasitol, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biochem, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Ctr Interdisciplinar Terapia Genica, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Pharmacol, BR-04023900 São Paulo, BrazilFAPESP: 06/61293-1Web of Science329-340engNeoplasia PressTranslational OncologyTissue Inhibitor of Metalloproteinase 1 Expression Associated with Gene Demethylation Confers Anoikis Resistance in Early Phases of Melanocyte Malignant Transformationinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP11600/319682022-11-04 15:20:28.0metadata only accessoai:repositorio.unifesp.br:11600/31968Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestopendoar:34652022-11-04T18:20:28Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.en.fl_str_mv |
Tissue Inhibitor of Metalloproteinase 1 Expression Associated with Gene Demethylation Confers Anoikis Resistance in Early Phases of Melanocyte Malignant Transformation |
title |
Tissue Inhibitor of Metalloproteinase 1 Expression Associated with Gene Demethylation Confers Anoikis Resistance in Early Phases of Melanocyte Malignant Transformation |
spellingShingle |
Tissue Inhibitor of Metalloproteinase 1 Expression Associated with Gene Demethylation Confers Anoikis Resistance in Early Phases of Melanocyte Malignant Transformation Ricca, Tatiana Iervolino [UNIFESP] |
title_short |
Tissue Inhibitor of Metalloproteinase 1 Expression Associated with Gene Demethylation Confers Anoikis Resistance in Early Phases of Melanocyte Malignant Transformation |
title_full |
Tissue Inhibitor of Metalloproteinase 1 Expression Associated with Gene Demethylation Confers Anoikis Resistance in Early Phases of Melanocyte Malignant Transformation |
title_fullStr |
Tissue Inhibitor of Metalloproteinase 1 Expression Associated with Gene Demethylation Confers Anoikis Resistance in Early Phases of Melanocyte Malignant Transformation |
title_full_unstemmed |
Tissue Inhibitor of Metalloproteinase 1 Expression Associated with Gene Demethylation Confers Anoikis Resistance in Early Phases of Melanocyte Malignant Transformation |
title_sort |
Tissue Inhibitor of Metalloproteinase 1 Expression Associated with Gene Demethylation Confers Anoikis Resistance in Early Phases of Melanocyte Malignant Transformation |
author |
Ricca, Tatiana Iervolino [UNIFESP] |
author_facet |
Ricca, Tatiana Iervolino [UNIFESP] Liang, Gangning Suenaga, Ana Paula Mitsue [UNIFESP] Han, Sang Won [UNIFESP] Jones, Peter A. Jasiulionis, Miriam Galvonas [UNIFESP] |
author_role |
author |
author2 |
Liang, Gangning Suenaga, Ana Paula Mitsue [UNIFESP] Han, Sang Won [UNIFESP] Jones, Peter A. Jasiulionis, Miriam Galvonas [UNIFESP] |
author2_role |
author author author author author |
dc.contributor.institution.none.fl_str_mv |
Universidade Federal de São Paulo (UNIFESP) Univ So Calif |
dc.contributor.author.fl_str_mv |
Ricca, Tatiana Iervolino [UNIFESP] Liang, Gangning Suenaga, Ana Paula Mitsue [UNIFESP] Han, Sang Won [UNIFESP] Jones, Peter A. Jasiulionis, Miriam Galvonas [UNIFESP] |
description |
Although anoikis resistance has been considered a hallmark of malignant phenotype, the causal relation between neoplastic transformation and anchorage-independent growth remains undefined. We developed an experimental model of murine melanocyte malignant transformation, where a melanocyte lineage (melan-a) was submitted to sequential cycles of anchorage blockade, resulting in progressive morphologic alterations, and malignant transformation. Throughout this process, cells corresponding to premalignant melanocytes and melanoma cell lines were established and show progressive anoikis resistance and increased expression of Timp1. in melan-a melanocytes, Timp1 expression is suppressed by DNA methylation as indicated by its reexpression after 5-aza-2'-deoxycytidine treatment. Methylation-sensitive single-nucleotide primer extension analysis showed increased demethylation in Timp1 in parallel with its expression along malignant transformation. Interestingly, TIMP1 expression has already been related with negative prognosis in some human cancers. Although described as aMMP inhibitor, this protein has been associated with apoptosis resistance in different cell types. Melan-a cells overexpressing Timp1 showed increased survival in suspension but were unable to form tumors in vivo, whereas Timp1-overexpressing melanoma cells showed reduced latency time for tumor appearance and increased metastatic potential. Here, we demonstrated for the first time an increment in Timp1 expression since the early phases of melanocyte malignant transformation, associated to a progressive gene demethylation, which confers anoikis resistance. in this way, Timp1 might be considered as a valued marker for melanocyte malignant transformation. |
publishDate |
2009 |
dc.date.issued.fl_str_mv |
2009-12-01 |
dc.date.accessioned.fl_str_mv |
2016-01-24T13:58:56Z |
dc.date.available.fl_str_mv |
2016-01-24T13:58:56Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
Translational Oncology. Ann Arbor: Neoplasia Press, v. 2, n. 4, p. 329-340, 2009. |
dc.identifier.uri.fl_str_mv |
http://repositorio.unifesp.br/handle/11600/31968 http://dx.doi.org/10.1593/tlo.09220 |
dc.identifier.issn.none.fl_str_mv |
1936-5233 |
dc.identifier.doi.none.fl_str_mv |
10.1593/tlo.09220 |
dc.identifier.wos.none.fl_str_mv |
WOS:000272551800018 |
identifier_str_mv |
Translational Oncology. Ann Arbor: Neoplasia Press, v. 2, n. 4, p. 329-340, 2009. 1936-5233 10.1593/tlo.09220 WOS:000272551800018 |
url |
http://repositorio.unifesp.br/handle/11600/31968 http://dx.doi.org/10.1593/tlo.09220 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.ispartof.none.fl_str_mv |
Translational Oncology |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
329-340 |
dc.publisher.none.fl_str_mv |
Neoplasia Press |
publisher.none.fl_str_mv |
Neoplasia Press |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UNIFESP instname:Universidade Federal de São Paulo (UNIFESP) instacron:UNIFESP |
instname_str |
Universidade Federal de São Paulo (UNIFESP) |
instacron_str |
UNIFESP |
institution |
UNIFESP |
reponame_str |
Repositório Institucional da UNIFESP |
collection |
Repositório Institucional da UNIFESP |
repository.name.fl_str_mv |
Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP) |
repository.mail.fl_str_mv |
|
_version_ |
1802764184685903872 |