Imunolocalização das proteínas Shh, Gli-1 e Fgf-2 em adenomas de células basais de glândulas salivares
Autor(a) principal: | |
---|---|
Data de Publicação: | 2015 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Repositório Institucional da UFU |
Texto Completo: | https://repositorio.ufu.br/handle/123456789/17023 https://doi.org/10.14393/ufu.di.2015.270 |
Resumo: | The basal cell adenoma (BCA) is a rare benign tumor of the salivary glands that primarily affects the parotid salivary gland. The causes and mechanisms involved in its pathogenesis are poorly understood. Researches have shown nuclear accumulation of β-Catenin in BCA. β-Catenin is related to the Wnt signaling pathway, but recent studies were not able to show activation of this pathway in BCA, suggesting that the its nuclear accumulation is not related to the presence of the Wnt pathway. The Hedgeghog (HH) signaling pathway has many interfaces with Wnt pathway, including ability to translocate β-Catenin to the nucleus and therefore activate cellular proliferation and it is known that excessive HH signaling pathway can lead to cancer and metastasis, but immunohistochemistry detection of proteins in this pathway was not yet studied in BCA. The aim of this study was to investigate the presence of proteins related to HH pathway in BCA, to improve the knowledge, the pathogenesis about this lesion and if it could relate to the nuclear accumulation of β-catenin. In 21 cases of BCA, by immunohistochemistry using streptavidin-biotin-peroxidase technique, we studied the proteins Shh, the main activator of the HH pathway, Gli-1, which is related to HH signal transduction, and also Fgf-2, an important inhibitor of cell proliferation induced by Shh in neuronal precursors and tumor cells, but in normal skin Fgf-2 showed an inductor role of Shh and β-catenin. Each reaction was analyzed qualitatively and quantitatively by QuickScore Index (QI). We found weak cytoplasmic reactivity in 71.4% of the cases to Shh, and 52.4% to Gli-1. Fgf-2 was observed varied cytoplasmic and nuclear staining in 100% of the cases. For all antigens, staining was similar in both luminal and abluminal cells. The average QI were 1.7, 1.6 and 8.5 to Shh, Gli-1 and Fgf-2, respectively. There was a positive correlation only between Shh and Fgf-2. Suggesting the existence of a positive feedback in which Fgf-2 has an inhibitory effect over Shh, showing a similar action to that found in neuronal precursors and tumor cells. These results do not confirm activation of the HH pathway in BCA, and is not related with the nuclear accumulation of β-catenin. But suggest that Fgf-2 has a tumor inducing action and also could represent the explanation of typical β-catenin found in this lesion. |
id |
UFU_d4c962ea74cba2efa9d8e97264616fd4 |
---|---|
oai_identifier_str |
oai:repositorio.ufu.br:123456789/17023 |
network_acronym_str |
UFU |
network_name_str |
Repositório Institucional da UFU |
repository_id_str |
|
spelling |
2016-06-22T18:47:39Z2016-02-172016-06-22T18:47:39Z2015-05-19NASCIMENTO NETO, Luiz Henrique. Imunolocalização das proteínas Shh, Gli-1 e Fgf-2 em adenomas de células basais de glândulas salivares. 2015. 49 f. Dissertação (Mestrado em Ciências da Saúde) - Universidade Federal de Uberlândia, Uberlândia, 2015. Disponível em: https://doi.org/10.14393/ufu.di.2015.270https://repositorio.ufu.br/handle/123456789/17023https://doi.org/10.14393/ufu.di.2015.270The basal cell adenoma (BCA) is a rare benign tumor of the salivary glands that primarily affects the parotid salivary gland. The causes and mechanisms involved in its pathogenesis are poorly understood. Researches have shown nuclear accumulation of β-Catenin in BCA. β-Catenin is related to the Wnt signaling pathway, but recent studies were not able to show activation of this pathway in BCA, suggesting that the its nuclear accumulation is not related to the presence of the Wnt pathway. The Hedgeghog (HH) signaling pathway has many interfaces with Wnt pathway, including ability to translocate β-Catenin to the nucleus and therefore activate cellular proliferation and it is known that excessive HH signaling pathway can lead to cancer and metastasis, but immunohistochemistry detection of proteins in this pathway was not yet studied in BCA. The aim of this study was to investigate the presence of proteins related to HH pathway in BCA, to improve the knowledge, the pathogenesis about this lesion and if it could relate to the nuclear accumulation of β-catenin. In 21 cases of BCA, by immunohistochemistry using streptavidin-biotin-peroxidase technique, we studied the proteins Shh, the main activator of the HH pathway, Gli-1, which is related to HH signal transduction, and also Fgf-2, an important inhibitor of cell proliferation induced by Shh in neuronal precursors and tumor cells, but in normal skin Fgf-2 showed an inductor role of Shh and β-catenin. Each reaction was analyzed qualitatively and quantitatively by QuickScore Index (QI). We found weak cytoplasmic reactivity in 71.4% of the cases to Shh, and 52.4% to Gli-1. Fgf-2 was observed varied cytoplasmic and nuclear staining in 100% of the cases. For all antigens, staining was similar in both luminal and abluminal cells. The average QI were 1.7, 1.6 and 8.5 to Shh, Gli-1 and Fgf-2, respectively. There was a positive correlation only between Shh and Fgf-2. Suggesting the existence of a positive feedback in which Fgf-2 has an inhibitory effect over Shh, showing a similar action to that found in neuronal precursors and tumor cells. These results do not confirm activation of the HH pathway in BCA, and is not related with the nuclear accumulation of β-catenin. But suggest that Fgf-2 has a tumor inducing action and also could represent the explanation of typical β-catenin found in this lesion.O adenoma de células basais (ACB) é uma neoplasia glandular benigna rara que acomete principalmente a glândula salivar parótida. As causas e mecanismos envolvidos na sua patogênese são pouco compreendidos. Pesquisas têm mostrado acúmulo nuclear de β-Catenina em ACB, tal proteína é fortemente relacionada à via de sinalização Wnt. Porém, estudos recentes mostraram ausência de ativadores dessa via em ACB, sugerindo que o acúmulo nuclear de β-Catenina não esteja relacionado com a presença da via Wnt. Sabe-se que existe uma relação entre a via de sinalização HH e a via Wnt e já foi demonstrado que sinalização excessiva da via HH pode levar ao câncer e a metástases, porém a detecção imunoistoquímica de proteínas dessa via em ACB ainda não foi objeto de estudo. Por isso, o objetivo desse estudo foi investigar se a ativação da via HH pudesse se relacionar com o acúmulo nuclear da β-Catenina em ACB, para melhor compreender a patogênese da lesão. Estudou-se a imunolocalização de duas proteínas envolvidas na via HH, a saber, Shh, principal ligante ativador da via, e Gli-1, proteína de transdução do sinal ativado, e ainda a Fgf-2, importante inibidor da proliferação celular induzida por Shh em precursores neuronais e células tumorais, porém, em pele normal apresentou-se como um indutor de Shh e β-Catenina. Foram analisados 21 casos de ACB, através de imunoistoquímica pela técnica de estreptavidina-biotina-peroxidase. Cada reação foi analisada qualitativamente e quantitativamente pelo índice de Quickscore (QI). Foi encontrado reatividade em 71,4% dos casos para Shh e em 52,4% para Gli-1, com predominância de marcação citoplasmática fraca. Enquanto que para Fgf-2 observou-se marcação citoplasmática e nuclear variada em 100% dos casos. A marcação foi semelhante tanto para células luminais e abluminais para todos os antígenos estudados. As médias de QI para Shh, Gli-1 e Fgf-2 foram de 1,7 ( 2,9), 1,6 ( 2,8) e 8,5 ( 5,5), respectivamente. Houve correlação positiva apenas entre Shh e Fgf-2, sugerindo a existência de um mecanismo de retroalimentação positiva, desta exercendo um efeito inibitório sobre aquela, apresentando uma ação semelhante ao encontrado em precursores neuronais e células tumorais. Tais resultados não confirmam a ativação da via HH e não se relaciona com o acúmulo nuclear da β-Catenina em ACB, podem sugerir que no ACB a Fgf-2 tenha ação de indutor tumoral e ainda representar a explicação do achado típico da β-Catenina no ACB.Mestre em Odontologiaapplication/pdfporUniversidade Federal de UberlândiaPrograma de Pós-graduação em OdontologiaUFUBRCiências da SaúdeAdenoma de células basaisVia de sinalização HHFgf-2Glândulas salivares - TumoresAdenomaBasal cell adenomaHH signaling pathwayCNPQ::CIENCIAS DA SAUDE::ODONTOLOGIAImunolocalização das proteínas Shh, Gli-1 e Fgf-2 em adenomas de células basais de glândulas salivaresinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisCardoso, Sérgio Vitorinohttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4769651D2Hiraki, Karen Renata Nakamurahttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4769485U1Rabelo, Gustavo Davihttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4716199E2http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4484374Y6Nascimento Neto, Luiz Henrique81759912e98bd0e6-1582-48c0-b833-cbcbe9e39448info:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFUinstname:Universidade Federal de Uberlândia (UFU)instacron:UFUTHUMBNAILImunolocalizacaoProteinasShh.pdf.jpgImunolocalizacaoProteinasShh.pdf.jpgGenerated Thumbnailimage/jpeg1212https://repositorio.ufu.br/bitstream/123456789/17023/3/ImunolocalizacaoProteinasShh.pdf.jpg692cd065a61e3ed9a181627de329206cMD53ORIGINALImunolocalizacaoProteinasShh.pdfapplication/pdf1338583https://repositorio.ufu.br/bitstream/123456789/17023/1/ImunolocalizacaoProteinasShh.pdf61c39f9d152ac9986ca40a4f6a309ec9MD51TEXTImunolocalizacaoProteinasShh.pdf.txtImunolocalizacaoProteinasShh.pdf.txtExtracted texttext/plain61439https://repositorio.ufu.br/bitstream/123456789/17023/2/ImunolocalizacaoProteinasShh.pdf.txt7bd3bd9705b934c7944e0b454bfd7958MD52123456789/170232021-09-15 14:36:02.149oai:repositorio.ufu.br:123456789/17023Repositório InstitucionalONGhttp://repositorio.ufu.br/oai/requestdiinf@dirbi.ufu.bropendoar:2021-09-15T17:36:02Repositório Institucional da UFU - Universidade Federal de Uberlândia (UFU)false |
dc.title.por.fl_str_mv |
Imunolocalização das proteínas Shh, Gli-1 e Fgf-2 em adenomas de células basais de glândulas salivares |
title |
Imunolocalização das proteínas Shh, Gli-1 e Fgf-2 em adenomas de células basais de glândulas salivares |
spellingShingle |
Imunolocalização das proteínas Shh, Gli-1 e Fgf-2 em adenomas de células basais de glândulas salivares Nascimento Neto, Luiz Henrique Adenoma de células basais Via de sinalização HH Fgf-2 Glândulas salivares - Tumores Adenoma Basal cell adenoma HH signaling pathway CNPQ::CIENCIAS DA SAUDE::ODONTOLOGIA |
title_short |
Imunolocalização das proteínas Shh, Gli-1 e Fgf-2 em adenomas de células basais de glândulas salivares |
title_full |
Imunolocalização das proteínas Shh, Gli-1 e Fgf-2 em adenomas de células basais de glândulas salivares |
title_fullStr |
Imunolocalização das proteínas Shh, Gli-1 e Fgf-2 em adenomas de células basais de glândulas salivares |
title_full_unstemmed |
Imunolocalização das proteínas Shh, Gli-1 e Fgf-2 em adenomas de células basais de glândulas salivares |
title_sort |
Imunolocalização das proteínas Shh, Gli-1 e Fgf-2 em adenomas de células basais de glândulas salivares |
author |
Nascimento Neto, Luiz Henrique |
author_facet |
Nascimento Neto, Luiz Henrique |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Cardoso, Sérgio Vitorino |
dc.contributor.advisor1Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4769651D2 |
dc.contributor.referee1.fl_str_mv |
Hiraki, Karen Renata Nakamura |
dc.contributor.referee1Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4769485U1 |
dc.contributor.referee2.fl_str_mv |
Rabelo, Gustavo Davi |
dc.contributor.referee2Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4716199E2 |
dc.contributor.authorLattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4484374Y6 |
dc.contributor.author.fl_str_mv |
Nascimento Neto, Luiz Henrique |
contributor_str_mv |
Cardoso, Sérgio Vitorino Hiraki, Karen Renata Nakamura Rabelo, Gustavo Davi |
dc.subject.por.fl_str_mv |
Adenoma de células basais Via de sinalização HH Fgf-2 Glândulas salivares - Tumores Adenoma |
topic |
Adenoma de células basais Via de sinalização HH Fgf-2 Glândulas salivares - Tumores Adenoma Basal cell adenoma HH signaling pathway CNPQ::CIENCIAS DA SAUDE::ODONTOLOGIA |
dc.subject.eng.fl_str_mv |
Basal cell adenoma HH signaling pathway |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS DA SAUDE::ODONTOLOGIA |
description |
The basal cell adenoma (BCA) is a rare benign tumor of the salivary glands that primarily affects the parotid salivary gland. The causes and mechanisms involved in its pathogenesis are poorly understood. Researches have shown nuclear accumulation of β-Catenin in BCA. β-Catenin is related to the Wnt signaling pathway, but recent studies were not able to show activation of this pathway in BCA, suggesting that the its nuclear accumulation is not related to the presence of the Wnt pathway. The Hedgeghog (HH) signaling pathway has many interfaces with Wnt pathway, including ability to translocate β-Catenin to the nucleus and therefore activate cellular proliferation and it is known that excessive HH signaling pathway can lead to cancer and metastasis, but immunohistochemistry detection of proteins in this pathway was not yet studied in BCA. The aim of this study was to investigate the presence of proteins related to HH pathway in BCA, to improve the knowledge, the pathogenesis about this lesion and if it could relate to the nuclear accumulation of β-catenin. In 21 cases of BCA, by immunohistochemistry using streptavidin-biotin-peroxidase technique, we studied the proteins Shh, the main activator of the HH pathway, Gli-1, which is related to HH signal transduction, and also Fgf-2, an important inhibitor of cell proliferation induced by Shh in neuronal precursors and tumor cells, but in normal skin Fgf-2 showed an inductor role of Shh and β-catenin. Each reaction was analyzed qualitatively and quantitatively by QuickScore Index (QI). We found weak cytoplasmic reactivity in 71.4% of the cases to Shh, and 52.4% to Gli-1. Fgf-2 was observed varied cytoplasmic and nuclear staining in 100% of the cases. For all antigens, staining was similar in both luminal and abluminal cells. The average QI were 1.7, 1.6 and 8.5 to Shh, Gli-1 and Fgf-2, respectively. There was a positive correlation only between Shh and Fgf-2. Suggesting the existence of a positive feedback in which Fgf-2 has an inhibitory effect over Shh, showing a similar action to that found in neuronal precursors and tumor cells. These results do not confirm activation of the HH pathway in BCA, and is not related with the nuclear accumulation of β-catenin. But suggest that Fgf-2 has a tumor inducing action and also could represent the explanation of typical β-catenin found in this lesion. |
publishDate |
2015 |
dc.date.issued.fl_str_mv |
2015-05-19 |
dc.date.accessioned.fl_str_mv |
2016-06-22T18:47:39Z |
dc.date.available.fl_str_mv |
2016-02-17 2016-06-22T18:47:39Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
NASCIMENTO NETO, Luiz Henrique. Imunolocalização das proteínas Shh, Gli-1 e Fgf-2 em adenomas de células basais de glândulas salivares. 2015. 49 f. Dissertação (Mestrado em Ciências da Saúde) - Universidade Federal de Uberlândia, Uberlândia, 2015. Disponível em: https://doi.org/10.14393/ufu.di.2015.270 |
dc.identifier.uri.fl_str_mv |
https://repositorio.ufu.br/handle/123456789/17023 |
dc.identifier.doi.por.fl_str_mv |
https://doi.org/10.14393/ufu.di.2015.270 |
identifier_str_mv |
NASCIMENTO NETO, Luiz Henrique. Imunolocalização das proteínas Shh, Gli-1 e Fgf-2 em adenomas de células basais de glândulas salivares. 2015. 49 f. Dissertação (Mestrado em Ciências da Saúde) - Universidade Federal de Uberlândia, Uberlândia, 2015. Disponível em: https://doi.org/10.14393/ufu.di.2015.270 |
url |
https://repositorio.ufu.br/handle/123456789/17023 https://doi.org/10.14393/ufu.di.2015.270 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Universidade Federal de Uberlândia |
dc.publisher.program.fl_str_mv |
Programa de Pós-graduação em Odontologia |
dc.publisher.initials.fl_str_mv |
UFU |
dc.publisher.country.fl_str_mv |
BR |
dc.publisher.department.fl_str_mv |
Ciências da Saúde |
publisher.none.fl_str_mv |
Universidade Federal de Uberlândia |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UFU instname:Universidade Federal de Uberlândia (UFU) instacron:UFU |
instname_str |
Universidade Federal de Uberlândia (UFU) |
instacron_str |
UFU |
institution |
UFU |
reponame_str |
Repositório Institucional da UFU |
collection |
Repositório Institucional da UFU |
bitstream.url.fl_str_mv |
https://repositorio.ufu.br/bitstream/123456789/17023/3/ImunolocalizacaoProteinasShh.pdf.jpg https://repositorio.ufu.br/bitstream/123456789/17023/1/ImunolocalizacaoProteinasShh.pdf https://repositorio.ufu.br/bitstream/123456789/17023/2/ImunolocalizacaoProteinasShh.pdf.txt |
bitstream.checksum.fl_str_mv |
692cd065a61e3ed9a181627de329206c 61c39f9d152ac9986ca40a4f6a309ec9 7bd3bd9705b934c7944e0b454bfd7958 |
bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 MD5 |
repository.name.fl_str_mv |
Repositório Institucional da UFU - Universidade Federal de Uberlândia (UFU) |
repository.mail.fl_str_mv |
diinf@dirbi.ufu.br |
_version_ |
1802110458139770880 |