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Title: MYC, FBXW7 and TP53 copy number variation and expression in Gastric Cancer
Authors: 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
Fed Univ Para
Universidade Federal de São Paulo (UNIFESP)
Universidade de São Paulo (USP)
Keywords: Gastric cancer
Issue Date: 23-Sep-2013
Publisher: Biomed Central Ltd
Citation: Bmc Gastroenterology. London: Biomed Central Ltd, v. 13, 10 p., 2013.
Abstract: 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.
ISSN: 1471-230X
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