Hyperthermia effects on Hsp27 and Hsp72 associations with mismatch repair (MMR) proteins and cisplatin toxicity in MMR-deficient/proficient colon cancer cell lines

Autores
Sottile Fleury, Mayra Lis; Losinno, Antonella Denise; Fanelli, Mariel Andrea; Cuello Carrión, Fernando Darío; Montt Guevara, Maria Magdalena; Vargas Roig, Laura Maria; Nadin, Silvina Beatriz
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Purpose: Hyperthermia is used in combination with conventional anticancer agents to potentiate their cytotoxicity. One of its key events is the synthesis of heat shock proteins (HSPs), which are able to associate with components from DNA repair mechanisms. However, little is known about their relationship with the mismatch repair system (MMR). Our aim was to study the effects of hyperthermia on cisplatin (cPt) sensitivity and to determine whether MLH1 and MSH2 associate with Hsp27 and Hsp72 in MMR-deficient(-)/-proficient(+) cells.Materials and methods: HCT116+ch2 (MMR-) and HCT116+ch3 (MMR+) cell lines were exposed to cPt with or without previous hyperthermia (42 °C, 1 h). Clonogenic survival assays, MTT, confocal immunofluorescence, immunoprecipitation, immunoblotting and flow cytometry were performed.Results: Hyperthermia increased the cPt resistance in MMR- cells 1.42-fold. Immunofluorescence revealed that after cPt, Hsp27 and Hsp72 translocated to the nucleus and colocalisation coefficients between these proteins with MLH1 and MSH2 increased in MMR+ cells. Immunoprecipitation confirmed the interactions between HSPs and MMR proteins in control and treated cells. Hyperthermia pretreatment induced cell cycle arrest, increased p73 expression and potentiated cPt sensitivity in MMR+ cells.Conclusions: This is the first report showing in a MMR-/+ cellular model that MLH1 and MSH2 are client proteins of Hsp27 and Hsp72. Our study suggests that p73 might participate in the cellular response to hyperthermia and cPt in a MMR-dependent manner. Further functional studies will confirm whether HSPs cooperate with the MMR system in cPt-induced DNA damage response or whether these protein interactions are only the result of their chaperone functions.
Fil: Sottile Fleury, Mayra Lis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Losinno, Antonella Denise. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina
Fil: Fanelli, Mariel Andrea. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina
Fil: Cuello Carrión, Fernando Darío. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Montt Guevara, Maria Magdalena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Vargas Roig, Laura Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina
Fil: Nadin, Silvina Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Materia
CHAPERONES
DNA DAMAGE/REPAIR
HEAT SHOCK RESPONSE
HT RADIO-CHEMOSENSITIZATION
THERMOTOLERANCE
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:11336/128681
Acceder
id CONICETDig_460c7a91ff48ef687e0ffabecaa3aa19
oai_identifier_str oai:ri.conicet.gov.ar:11336/128681
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Hyperthermia effects on Hsp27 and Hsp72 associations with mismatch repair (MMR) proteins and cisplatin toxicity in MMR-deficient/proficient colon cancer cell linesSottile Fleury, Mayra LisLosinno, Antonella DeniseFanelli, Mariel AndreaCuello Carrión, Fernando DaríoMontt Guevara, Maria MagdalenaVargas Roig, Laura MariaNadin, Silvina BeatrizCHAPERONESDNA DAMAGE/REPAIRHEAT SHOCK RESPONSEHT RADIO-CHEMOSENSITIZATIONTHERMOTOLERANCEhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Purpose: Hyperthermia is used in combination with conventional anticancer agents to potentiate their cytotoxicity. One of its key events is the synthesis of heat shock proteins (HSPs), which are able to associate with components from DNA repair mechanisms. However, little is known about their relationship with the mismatch repair system (MMR). Our aim was to study the effects of hyperthermia on cisplatin (cPt) sensitivity and to determine whether MLH1 and MSH2 associate with Hsp27 and Hsp72 in MMR-deficient(-)/-proficient(+) cells.Materials and methods: HCT116+ch2 (MMR-) and HCT116+ch3 (MMR+) cell lines were exposed to cPt with or without previous hyperthermia (42 °C, 1 h). Clonogenic survival assays, MTT, confocal immunofluorescence, immunoprecipitation, immunoblotting and flow cytometry were performed.Results: Hyperthermia increased the cPt resistance in MMR- cells 1.42-fold. Immunofluorescence revealed that after cPt, Hsp27 and Hsp72 translocated to the nucleus and colocalisation coefficients between these proteins with MLH1 and MSH2 increased in MMR+ cells. Immunoprecipitation confirmed the interactions between HSPs and MMR proteins in control and treated cells. Hyperthermia pretreatment induced cell cycle arrest, increased p73 expression and potentiated cPt sensitivity in MMR+ cells.Conclusions: This is the first report showing in a MMR-/+ cellular model that MLH1 and MSH2 are client proteins of Hsp27 and Hsp72. Our study suggests that p73 might participate in the cellular response to hyperthermia and cPt in a MMR-dependent manner. Further functional studies will confirm whether HSPs cooperate with the MMR system in cPt-induced DNA damage response or whether these protein interactions are only the result of their chaperone functions.Fil: Sottile Fleury, Mayra Lis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Losinno, Antonella Denise. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; ArgentinaFil: Fanelli, Mariel Andrea. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; ArgentinaFil: Cuello Carrión, Fernando Darío. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Montt Guevara, Maria Magdalena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Vargas Roig, Laura Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; ArgentinaFil: Nadin, Silvina Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaInforma Healthcare2015-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/128681Sottile Fleury, Mayra Lis; Losinno, Antonella Denise; Fanelli, Mariel Andrea; Cuello Carrión, Fernando Darío; Montt Guevara, Maria Magdalena; et al.; Hyperthermia effects on Hsp27 and Hsp72 associations with mismatch repair (MMR) proteins and cisplatin toxicity in MMR-deficient/proficient colon cancer cell lines; Informa Healthcare; International Journal Of Hyperthermia; 31; 5; 7-2015; 464-4750265-6736CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.3109/02656736.2015.1026848info:eu-repo/semantics/altIdentifier/url/https://www.tandfonline.com/doi/full/10.3109/02656736.2015.1026848info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:41:40Zoai:ri.conicet.gov.ar:11336/128681instacron: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 09:41:40.646CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Hyperthermia effects on Hsp27 and Hsp72 associations with mismatch repair (MMR) proteins and cisplatin toxicity in MMR-deficient/proficient colon cancer cell lines
title Hyperthermia effects on Hsp27 and Hsp72 associations with mismatch repair (MMR) proteins and cisplatin toxicity in MMR-deficient/proficient colon cancer cell lines
spellingShingle Hyperthermia effects on Hsp27 and Hsp72 associations with mismatch repair (MMR) proteins and cisplatin toxicity in MMR-deficient/proficient colon cancer cell lines
Sottile Fleury, Mayra Lis
CHAPERONES
DNA DAMAGE/REPAIR
HEAT SHOCK RESPONSE
HT RADIO-CHEMOSENSITIZATION
THERMOTOLERANCE
title_short Hyperthermia effects on Hsp27 and Hsp72 associations with mismatch repair (MMR) proteins and cisplatin toxicity in MMR-deficient/proficient colon cancer cell lines
title_full Hyperthermia effects on Hsp27 and Hsp72 associations with mismatch repair (MMR) proteins and cisplatin toxicity in MMR-deficient/proficient colon cancer cell lines
title_fullStr Hyperthermia effects on Hsp27 and Hsp72 associations with mismatch repair (MMR) proteins and cisplatin toxicity in MMR-deficient/proficient colon cancer cell lines
title_full_unstemmed Hyperthermia effects on Hsp27 and Hsp72 associations with mismatch repair (MMR) proteins and cisplatin toxicity in MMR-deficient/proficient colon cancer cell lines
title_sort Hyperthermia effects on Hsp27 and Hsp72 associations with mismatch repair (MMR) proteins and cisplatin toxicity in MMR-deficient/proficient colon cancer cell lines
dc.creator.none.fl_str_mv Sottile Fleury, Mayra Lis
Losinno, Antonella Denise
Fanelli, Mariel Andrea
Cuello Carrión, Fernando Darío
Montt Guevara, Maria Magdalena
Vargas Roig, Laura Maria
Nadin, Silvina Beatriz
author Sottile Fleury, Mayra Lis
author_facet Sottile Fleury, Mayra Lis
Losinno, Antonella Denise
Fanelli, Mariel Andrea
Cuello Carrión, Fernando Darío
Montt Guevara, Maria Magdalena
Vargas Roig, Laura Maria
Nadin, Silvina Beatriz
author_role author
author2 Losinno, Antonella Denise
Fanelli, Mariel Andrea
Cuello Carrión, Fernando Darío
Montt Guevara, Maria Magdalena
Vargas Roig, Laura Maria
Nadin, Silvina Beatriz
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv CHAPERONES
DNA DAMAGE/REPAIR
HEAT SHOCK RESPONSE
HT RADIO-CHEMOSENSITIZATION
THERMOTOLERANCE
topic CHAPERONES
DNA DAMAGE/REPAIR
HEAT SHOCK RESPONSE
HT RADIO-CHEMOSENSITIZATION
THERMOTOLERANCE
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Purpose: Hyperthermia is used in combination with conventional anticancer agents to potentiate their cytotoxicity. One of its key events is the synthesis of heat shock proteins (HSPs), which are able to associate with components from DNA repair mechanisms. However, little is known about their relationship with the mismatch repair system (MMR). Our aim was to study the effects of hyperthermia on cisplatin (cPt) sensitivity and to determine whether MLH1 and MSH2 associate with Hsp27 and Hsp72 in MMR-deficient(-)/-proficient(+) cells.Materials and methods: HCT116+ch2 (MMR-) and HCT116+ch3 (MMR+) cell lines were exposed to cPt with or without previous hyperthermia (42 °C, 1 h). Clonogenic survival assays, MTT, confocal immunofluorescence, immunoprecipitation, immunoblotting and flow cytometry were performed.Results: Hyperthermia increased the cPt resistance in MMR- cells 1.42-fold. Immunofluorescence revealed that after cPt, Hsp27 and Hsp72 translocated to the nucleus and colocalisation coefficients between these proteins with MLH1 and MSH2 increased in MMR+ cells. Immunoprecipitation confirmed the interactions between HSPs and MMR proteins in control and treated cells. Hyperthermia pretreatment induced cell cycle arrest, increased p73 expression and potentiated cPt sensitivity in MMR+ cells.Conclusions: This is the first report showing in a MMR-/+ cellular model that MLH1 and MSH2 are client proteins of Hsp27 and Hsp72. Our study suggests that p73 might participate in the cellular response to hyperthermia and cPt in a MMR-dependent manner. Further functional studies will confirm whether HSPs cooperate with the MMR system in cPt-induced DNA damage response or whether these protein interactions are only the result of their chaperone functions.
Fil: Sottile Fleury, Mayra Lis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Losinno, Antonella Denise. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina
Fil: Fanelli, Mariel Andrea. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina
Fil: Cuello Carrión, Fernando Darío. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Montt Guevara, Maria Magdalena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Vargas Roig, Laura Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina
Fil: Nadin, Silvina Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
description Purpose: Hyperthermia is used in combination with conventional anticancer agents to potentiate their cytotoxicity. One of its key events is the synthesis of heat shock proteins (HSPs), which are able to associate with components from DNA repair mechanisms. However, little is known about their relationship with the mismatch repair system (MMR). Our aim was to study the effects of hyperthermia on cisplatin (cPt) sensitivity and to determine whether MLH1 and MSH2 associate with Hsp27 and Hsp72 in MMR-deficient(-)/-proficient(+) cells.Materials and methods: HCT116+ch2 (MMR-) and HCT116+ch3 (MMR+) cell lines were exposed to cPt with or without previous hyperthermia (42 °C, 1 h). Clonogenic survival assays, MTT, confocal immunofluorescence, immunoprecipitation, immunoblotting and flow cytometry were performed.Results: Hyperthermia increased the cPt resistance in MMR- cells 1.42-fold. Immunofluorescence revealed that after cPt, Hsp27 and Hsp72 translocated to the nucleus and colocalisation coefficients between these proteins with MLH1 and MSH2 increased in MMR+ cells. Immunoprecipitation confirmed the interactions between HSPs and MMR proteins in control and treated cells. Hyperthermia pretreatment induced cell cycle arrest, increased p73 expression and potentiated cPt sensitivity in MMR+ cells.Conclusions: This is the first report showing in a MMR-/+ cellular model that MLH1 and MSH2 are client proteins of Hsp27 and Hsp72. Our study suggests that p73 might participate in the cellular response to hyperthermia and cPt in a MMR-dependent manner. Further functional studies will confirm whether HSPs cooperate with the MMR system in cPt-induced DNA damage response or whether these protein interactions are only the result of their chaperone functions.
publishDate 2015
dc.date.none.fl_str_mv 2015-07
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/11336/128681
Sottile Fleury, Mayra Lis; Losinno, Antonella Denise; Fanelli, Mariel Andrea; Cuello Carrión, Fernando Darío; Montt Guevara, Maria Magdalena; et al.; Hyperthermia effects on Hsp27 and Hsp72 associations with mismatch repair (MMR) proteins and cisplatin toxicity in MMR-deficient/proficient colon cancer cell lines; Informa Healthcare; International Journal Of Hyperthermia; 31; 5; 7-2015; 464-475
0265-6736
CONICET Digital
CONICET
url http://hdl.handle.net/11336/128681
identifier_str_mv Sottile Fleury, Mayra Lis; Losinno, Antonella Denise; Fanelli, Mariel Andrea; Cuello Carrión, Fernando Darío; Montt Guevara, Maria Magdalena; et al.; Hyperthermia effects on Hsp27 and Hsp72 associations with mismatch repair (MMR) proteins and cisplatin toxicity in MMR-deficient/proficient colon cancer cell lines; Informa Healthcare; International Journal Of Hyperthermia; 31; 5; 7-2015; 464-475
0265-6736
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.3109/02656736.2015.1026848
info:eu-repo/semantics/altIdentifier/url/https://www.tandfonline.com/doi/full/10.3109/02656736.2015.1026848
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
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dc.publisher.none.fl_str_mv Informa Healthcare
publisher.none.fl_str_mv Informa Healthcare
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
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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score 13.070432

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