Assessment of differential expression of oncogenes in adenocarcinoma of stomach with fluorescent labeling and simultaneous amplification of gene transcripts

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Assessment of differential expression of oncogenes in adenocarcinoma of stomach with fluorescent labeling and simultaneous amplification of gene transcripts

Background. Gastric cancer is one of the leading malignancies with a poor prognosis and low survival rates. Although the mechanisms underlying its development are still unknown, there is a consensus that genetic instability, inactivation of tumor suppressor genes and over-expression of oncogenes are involved in the early and late stages of gastric carcinogenesis. In the present study we wanted to display differential expression of seven oncogenes, namely CCNE1, EGF, ERBB3, FGF4, HRG1, HGFR and TDGF1.

Patients and methods. We employed a method based on the multiplex reverse transcription polymerase chain (RT-PCR) method with a fluorescence detection.

Results. More than half of patients (74.3%) out of total 74 with gastric adenocarcinoma had over-expressed at least one oncogene, with the exception of FGF4, which was expressed in tumor tissue of less than one third of patients. 56.8% of the patients patients showed over-expression of two or more oncogenes.

Conclusions. Patients with precancerous lesions had elevated levels of TDGF1 or cripto-1 (64.9%) and CCNE1 (57.1%), suggesting that they could be used as markers for an early detection of malignant changes in stomach. Finally, the fluorescent multiplex RT-PCR method could be of value for rapid assessment of oncogene mRNA levels in small samples of tumor or precancerous biopsies.

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  • Ferlay J. Globocan 2000: Cancer incidence mortality and prevalence worldwide. Lyon: IARC Press; 2001: 1 CD-ROM.

  • Lauren P. The two histological main types of gastric carcinoma: diffuse and so-called intestinal-type carcinoma. An attempt at a histo-clinical classification. Acta Pathol Microbiol Scand 1965; 64: 31-49.

  • Zheng L Wang L Ajani J Xie K. Molecular basis of gastric cancer development and progression. Gastric Cancer 2004; 72: 61-77.

  • Kufe DW Holland JF Frei E Abramson DH Dang CT DeAngelis LM et al. Cancer medicine 6. Hamilton Ont.: BC Decker; 2003.

  • Barletta C Scillato F Sega FM Mannella E. Genetic alteration in gastrointestinal cancer. A molecular and cytogenetic study. Anticancer Res 1993; 136A: 2325-9.

  • Tahara E. Genetic pathways of two types of gastric cancer. IARC Sci Publ 2004; 157: 327-49.

  • Engelman JA Zejnullahu K Mitsudomi T Song Y Hyland C Park JO et al. MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science 2007; 316(5827): 1039-43.

  • Smolen GA Sordella R Muir B Mohapatra G Barmettler A Archibald H et al. Amplification of MET may identify a subset of cancers with extreme sensitivity to the selective tyrosine kinase inhibitor PHA-665752. Proc Natl Acad Sci USA 2006; 103(7): 2316-21.

  • Uen YH Lin SR Wu CH Hsieh JS Lu CY Yu FJ et al. Clinical significance of MUC1 and c-Met RT-PCR detection of circulating tumor cells in patients with gastric carcinoma. Clin Chim Acta 2006; 367(1-2): 55-61.

  • Corso S Comoglio PM Giordano S. Cancer therapy: can the challenge be MET? Trends Mol Med 2005; 11(6): 84-92.

  • Felsher DW. Cancer revoked: oncogenes as therapeutic targets. Nat Rev Cancer 2003; 3(5): 375-80.

  • Kataoka H Joh T Kasugai K Okayama N Moriyama A Asai K et al. Expression of mRNA for heregulin and its receptor ErbB-3 and ErbB-4 in human upper gastrointestinal mucosa. Life Sci 1998; 63(7): 553-64.

  • Bachmair F Huber C Daxenbichler G. Quanititation of gene expression by means of HPLC analysis of RT-PCR products. Clin Chim Acta 1999; 279(1-2): 25-34.

  • Huber CG. Micropellicular stationary phases for high-performance liquid chromatography of double-stranded DNA. J Chromatogr A 1998; 806: 3-30.

  • Heideman DA Snijders PJ Bloemena E Meijer CJ Offerhaus GJ Meuwissen SG et al. Absence of tpr-met and expression of c-met in human gastric mucosa and carcinoma. J Pathol 2001; 194(4): 428-35.

  • Nakajima M Sawada H Yamada Y Watanabe A Tatsumi M Yamashita J et al. The prognostic significance of amplification and overexpression of c-met and c-erb B-2 in human gastric carcinomas. Cancer 1999; 85(9): 1894-902.

  • Rasola A Fassetta M De Bacco F D'Alessandro L Gramaglia D Di Renzo MF et al. A positive feedback loop between hepatocyte growth factor receptor and beta-catenin sustains colorectal cancer cell invasive growth. Oncogene 2007; 26(7): 1078-87.

  • Bianco C Adkins HB Wechselberger C Seno M Normanno N De Luca A et al. Cripto-1 activates nodal- and ALK4-dependent and -independent signaling pathways in mammary epithelial Cells. Mol Cell Biol 2002; 22(8): 2586-97.

  • Bianco C Strizzi L Mancino M Rehman A Hamada S Watanabe K et al. Identification of cripto-1 as a novel serologic marker for breast and colon cancer. Clin Cancer Res 2006; 12(17): 5158-64.

  • Hamada S Watanabe K Hirota M Bianco C Strizzi L Mancino M et al. beta-Catenin/TCF/LEF regulate expression of the short form human Cripto-1. Biochem Biophys Res Commun 2007; 355(1): 240-4.

  • Minchiotti G. Nodal-dependant Cripto signaling in ES cells: from stem cells to tumor biology. Oncogene 2005; 24(37): 5668-75.

  • Haruma K Ito M Kohmoto K Kamada T Kitada Y Yasui W et al. Expression of cell cycle regulators and growth factor/receptor systems in gastric carcinoma in young adults: association with Helicobacter pylori infection. Int J Mol Med 2000; 5(2): 185-90.

  • Akama Y Yasui W Yokozaki H Kuniyasu H Kitahara K Ishikawa T et al. Frequent amplification of the cyclin E gene in human gastric carcinomas. Jpn J Cancer Res 1995; 86(7): 617-21.

  • Tenderenda M. A study on the prognostic value of cyclins D1 and E expression levels in resectable gastric cancer and on some correlations between cyclins expression histoclinical parameters and selected protein products of cell-cycle regulatory genes. J Exp Clin Cancer Res 2005; 24(3): 405-14.

  • Yasui W Oue N Aung PP Matsumura S Shutoh M Nakayama H. Molecular-pathological prognostic factors of gastric cancer: a review. Gastric Cancer 2005; 8(2): 86-94.

  • Yu J Miehlke S Ebert MP Szokodi D Wehvnignh B Malfertheiner P et al. Expression of cyclin genes in human gastric cancer and in first degree relatives. Chin Med J (Engl) 2002; 115(5): 710-5.

  • Breuleux M. Role of heregulin in human cancer. Cell Mol Life Sci 2007; 64(18): 2358-77.

  • Kobayashi M Iwamatsu A Shinohara-Kanda A Ihara S Fukui Y. Activation of ErbB3-PI3-kinase pathway is correlated with malignant phenotypes of adenocarcinomas. Oncogene 2003; 22(9): 1294-301.

  • Slesak B Harlozinska A Porebska I Bojarowski T Lapinska J Rzeszutko M et al. Expression of epidermal growth factor receptor family proteins (EGFR c-erbB-2 and c-erbB-3) in gastric cancer and chronic gastritis. Anticancer Res 1998; 18(4A): 2727-32.

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