MYC, FBXW7 and TP53 copy number variation and expression in Gastric Cancer

Detalhes bibliográficos
Autor(a) principal: Calcagno, Danielle Queiroz [UNIFESP]
Data de Publicação: 2013
Outros Autores: Freitas, Vanessa Morais, Leal, Mariana Ferreira [UNIFESP], Souza, Carolina Rosal Teixeira de, Demachki, Samia, Montenegro, Raquel, Assumpcao, Paulo Pimentel, Khayat, Andre Salim, Smith, Marilia de Arruda Cardoso [UNIFESP], Santos, Andrea Kely Campos Ribeiro dos, Burbano, Rommel Rodriguez
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNIFESP
Texto Completo: http://dx.doi.org/10.1186/1471-230X-13-141
http://repositorio.unifesp.br/handle/11600/36764
Resumo: Background: MYC deregulation is a common event in gastric carcinogenesis, usually as a consequence of gene amplification, chromosomal translocations, or posttranslational mechanisms. FBXW7 is a p53-controlled tumor-suppressor that plays a role in the regulation of cell cycle exit and reentry via MYC degradation.Methods: We evaluated MYC, FBXW7, and TP53 copy number, mRNA levels, and protein expression in gastric cancer and paired non-neoplastic specimens from 33 patients and also in gastric adenocarcinoma cell lines. We also determined the invasion potential of the gastric cancer cell lines.Results: MYC amplification was observed in 51.5% of gastric tumor samples. Deletion of one copy of FBXW7 and TP53 was observed in 45.5% and 21.2% of gastric tumors, respectively. MYC mRNA expression was significantly higher in tumors than in non-neoplastic samples. FBXW7 and TP53 mRNA expression was markedly lower in tumors than in paired non-neoplastic specimens. Moreover, deregulated MYC and FBXW7 mRNA expression was associated with the presence of lymph node metastasis and tumor stage III-IV. Additionally, MYC immunostaining was more frequently observed in intestinal-type than diffuse-type gastric cancers and was associated with MYC mRNA expression. in vitro studies showed that increased MYC and reduced FBXW7 expression is associated with a more invasive phenotype in gastric cancer cell lines. This result encouraged us to investigate the activity of the gelatinases MMP-2 and MMP-9 in both cell lines. Both gelatinases are synthesized predominantly by stromal cells rather than cancer cells, and it has been proposed that both contribute to cancer progression. We observed a significant increase in MMP-9 activity in ACP02 compared with ACP03 cells. These results confirmed that ACP02 cells have greater invasion capability than ACP03 cells.Conclusion: in conclusion, FBXW7 and MYC mRNA may play a role in aggressive biologic behavior of gastric cancer cells and may be a useful indicator of poor prognosis. Furthermore, MYC is a candidate target for new therapies against gastric cancer.
id UFSP_918aaf3aacf438deeb12da4952d26968
oai_identifier_str oai:repositorio.unifesp.br/:11600/36764
network_acronym_str UFSP
network_name_str Repositório Institucional da UNIFESP
repository_id_str 3465
spelling MYC, FBXW7 and TP53 copy number variation and expression in Gastric CancerGastric cancerMYCFBXW7TP53Background: MYC deregulation is a common event in gastric carcinogenesis, usually as a consequence of gene amplification, chromosomal translocations, or posttranslational mechanisms. FBXW7 is a p53-controlled tumor-suppressor that plays a role in the regulation of cell cycle exit and reentry via MYC degradation.Methods: We evaluated MYC, FBXW7, and TP53 copy number, mRNA levels, and protein expression in gastric cancer and paired non-neoplastic specimens from 33 patients and also in gastric adenocarcinoma cell lines. We also determined the invasion potential of the gastric cancer cell lines.Results: MYC amplification was observed in 51.5% of gastric tumor samples. Deletion of one copy of FBXW7 and TP53 was observed in 45.5% and 21.2% of gastric tumors, respectively. MYC mRNA expression was significantly higher in tumors than in non-neoplastic samples. FBXW7 and TP53 mRNA expression was markedly lower in tumors than in paired non-neoplastic specimens. Moreover, deregulated MYC and FBXW7 mRNA expression was associated with the presence of lymph node metastasis and tumor stage III-IV. Additionally, MYC immunostaining was more frequently observed in intestinal-type than diffuse-type gastric cancers and was associated with MYC mRNA expression. in vitro studies showed that increased MYC and reduced FBXW7 expression is associated with a more invasive phenotype in gastric cancer cell lines. This result encouraged us to investigate the activity of the gelatinases MMP-2 and MMP-9 in both cell lines. Both gelatinases are synthesized predominantly by stromal cells rather than cancer cells, and it has been proposed that both contribute to cancer progression. We observed a significant increase in MMP-9 activity in ACP02 compared with ACP03 cells. These results confirmed that ACP02 cells have greater invasion capability than ACP03 cells.Conclusion: in conclusion, FBXW7 and MYC mRNA may play a role in aggressive biologic behavior of gastric cancer cells and may be a useful indicator of poor prognosis. Furthermore, MYC is a candidate target for new therapies against gastric cancer.Fed Univ Para, Inst Ciencias Biol, Lab Citogenet Humana, BR-66059 Belem, Para, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Morfol & Genet, Disciplina Genet, BR-04023900 São Paulo, SP, BrazilUniv São Paulo, Inst Ciencias Biomed, Dept Biol Celular & Desenvolvimento, São Paulo, SP, BrazilFed Univ Para, Hosp Univ Joao Barros Barreto, Fac Med, Lab Imunoistoquim,Serv Anat Patol, BR-66059 Belem, PA, BrazilFed Univ Para, Hosp Univ Joao Barros Barreto, Serv Cirurgia, BR-66059 Belem, PA, BrazilFed Univ Para, Inst Ciencias Biol, Lab Genet Humana, BR-66059 Belem, PA, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Morfol & Genet, Disciplina Genet, BR-04023900 São Paulo, SP, BrazilWeb of ScienceConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Biomed Central LtdFed Univ ParaUniversidade Federal de São Paulo (UNIFESP)Universidade de São Paulo (USP)Calcagno, Danielle Queiroz [UNIFESP]Freitas, Vanessa MoraisLeal, Mariana Ferreira [UNIFESP]Souza, Carolina Rosal Teixeira deDemachki, SamiaMontenegro, RaquelAssumpcao, Paulo PimentelKhayat, Andre SalimSmith, Marilia de Arruda Cardoso [UNIFESP]Santos, Andrea Kely Campos Ribeiro dosBurbano, Rommel Rodriguez2016-01-24T14:34:26Z2016-01-24T14:34:26Z2013-09-23info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion10application/pdfhttp://dx.doi.org/10.1186/1471-230X-13-141Bmc Gastroenterology. London: Biomed Central Ltd, v. 13, 10 p., 2013.10.1186/1471-230X-13-141WOS000325805400001.pdf1471-230Xhttp://repositorio.unifesp.br/handle/11600/36764WOS:000325805400001engBmc Gastroenterologyinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP2024-08-08T02:15:59Zoai:repositorio.unifesp.br/:11600/36764Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestbiblioteca.csp@unifesp.bropendoar:34652024-08-08T02:15:59Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false
dc.title.none.fl_str_mv MYC, FBXW7 and TP53 copy number variation and expression in Gastric Cancer
title MYC, FBXW7 and TP53 copy number variation and expression in Gastric Cancer
spellingShingle MYC, FBXW7 and TP53 copy number variation and expression in Gastric Cancer
Calcagno, Danielle Queiroz [UNIFESP]
Gastric cancer
MYC
FBXW7
TP53
title_short MYC, FBXW7 and TP53 copy number variation and expression in Gastric Cancer
title_full MYC, FBXW7 and TP53 copy number variation and expression in Gastric Cancer
title_fullStr MYC, FBXW7 and TP53 copy number variation and expression in Gastric Cancer
title_full_unstemmed MYC, FBXW7 and TP53 copy number variation and expression in Gastric Cancer
title_sort MYC, FBXW7 and TP53 copy number variation and expression in Gastric Cancer
author Calcagno, Danielle Queiroz [UNIFESP]
author_facet Calcagno, Danielle Queiroz [UNIFESP]
Freitas, Vanessa Morais
Leal, Mariana Ferreira [UNIFESP]
Souza, Carolina Rosal Teixeira de
Demachki, Samia
Montenegro, Raquel
Assumpcao, Paulo Pimentel
Khayat, Andre Salim
Smith, Marilia de Arruda Cardoso [UNIFESP]
Santos, Andrea Kely Campos Ribeiro dos
Burbano, Rommel Rodriguez
author_role author
author2 Freitas, Vanessa Morais
Leal, Mariana Ferreira [UNIFESP]
Souza, Carolina Rosal Teixeira de
Demachki, Samia
Montenegro, Raquel
Assumpcao, Paulo Pimentel
Khayat, Andre Salim
Smith, Marilia de Arruda Cardoso [UNIFESP]
Santos, Andrea Kely Campos Ribeiro dos
Burbano, Rommel Rodriguez
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Fed Univ Para
Universidade Federal de São Paulo (UNIFESP)
Universidade de São Paulo (USP)
dc.contributor.author.fl_str_mv Calcagno, Danielle Queiroz [UNIFESP]
Freitas, Vanessa Morais
Leal, Mariana Ferreira [UNIFESP]
Souza, Carolina Rosal Teixeira de
Demachki, Samia
Montenegro, Raquel
Assumpcao, Paulo Pimentel
Khayat, Andre Salim
Smith, Marilia de Arruda Cardoso [UNIFESP]
Santos, Andrea Kely Campos Ribeiro dos
Burbano, Rommel Rodriguez
dc.subject.por.fl_str_mv Gastric cancer
MYC
FBXW7
TP53
topic Gastric cancer
MYC
FBXW7
TP53
description Background: MYC deregulation is a common event in gastric carcinogenesis, usually as a consequence of gene amplification, chromosomal translocations, or posttranslational mechanisms. FBXW7 is a p53-controlled tumor-suppressor that plays a role in the regulation of cell cycle exit and reentry via MYC degradation.Methods: We evaluated MYC, FBXW7, and TP53 copy number, mRNA levels, and protein expression in gastric cancer and paired non-neoplastic specimens from 33 patients and also in gastric adenocarcinoma cell lines. We also determined the invasion potential of the gastric cancer cell lines.Results: MYC amplification was observed in 51.5% of gastric tumor samples. Deletion of one copy of FBXW7 and TP53 was observed in 45.5% and 21.2% of gastric tumors, respectively. MYC mRNA expression was significantly higher in tumors than in non-neoplastic samples. FBXW7 and TP53 mRNA expression was markedly lower in tumors than in paired non-neoplastic specimens. Moreover, deregulated MYC and FBXW7 mRNA expression was associated with the presence of lymph node metastasis and tumor stage III-IV. Additionally, MYC immunostaining was more frequently observed in intestinal-type than diffuse-type gastric cancers and was associated with MYC mRNA expression. in vitro studies showed that increased MYC and reduced FBXW7 expression is associated with a more invasive phenotype in gastric cancer cell lines. This result encouraged us to investigate the activity of the gelatinases MMP-2 and MMP-9 in both cell lines. Both gelatinases are synthesized predominantly by stromal cells rather than cancer cells, and it has been proposed that both contribute to cancer progression. We observed a significant increase in MMP-9 activity in ACP02 compared with ACP03 cells. These results confirmed that ACP02 cells have greater invasion capability than ACP03 cells.Conclusion: in conclusion, FBXW7 and MYC mRNA may play a role in aggressive biologic behavior of gastric cancer cells and may be a useful indicator of poor prognosis. Furthermore, MYC is a candidate target for new therapies against gastric cancer.
publishDate 2013
dc.date.none.fl_str_mv 2013-09-23
2016-01-24T14:34:26Z
2016-01-24T14:34:26Z
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.1186/1471-230X-13-141
Bmc Gastroenterology. London: Biomed Central Ltd, v. 13, 10 p., 2013.
10.1186/1471-230X-13-141
WOS000325805400001.pdf
1471-230X
http://repositorio.unifesp.br/handle/11600/36764
WOS:000325805400001
url http://dx.doi.org/10.1186/1471-230X-13-141
http://repositorio.unifesp.br/handle/11600/36764
identifier_str_mv Bmc Gastroenterology. London: Biomed Central Ltd, v. 13, 10 p., 2013.
10.1186/1471-230X-13-141
WOS000325805400001.pdf
1471-230X
WOS:000325805400001
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Bmc Gastroenterology
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 10
application/pdf
dc.publisher.none.fl_str_mv Biomed Central Ltd
publisher.none.fl_str_mv Biomed Central Ltd
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 biblioteca.csp@unifesp.br
_version_ 1814268380865101824