MYC, FBXW7 and TP53 copy number variation and expression in Gastric Cancer
Autor(a) principal: | |
---|---|
Data de Publicação: | 2013 |
Outros Autores: | , , , , , , , , , |
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 |