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Journal of Cancer Research and Clinical Oncology

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01-08-2010 | Original Paper

Potential roles for PA28β in gastric adenocarcinoma development and diagnosis

Authors: Qiaojia Huang, Qingling Huang, Wansong Lin, Jianyin Lin, Xu Lin

Published in: Journal of Cancer Research and Clinical Oncology | Issue 8/2010

Abstract

Purpose

This study aimed to investigate the expression level of human proteasome activator PA28β subunit (PA28β) in gastric adenocarcinomas (GA) tissues and investigate its potential role in GA carcinogenesis.

Methods

To investigate the expression profile of PA28β in patients with GA, we employed immunohistochemistry for detection of 287 cases of paired GA and adjacent non-neoplastic tissues. To evaluate the role of PA28β in GA cells, we measured cell growth, colony formation, soft agar, and nude mice tumorigenicity assays in MKN-45 GA cells pre- and post-PA28β transfection.

Results

PA28β had lower expression in 183 of 287 GA cases compared to paired normal samples (63.76%; P ≤ 0.001). Decreased expression was dependent on histological type, TNM stage, and differentiation grade. Significantly decreased expression was correlated with a diffuse histological type (88/116, 75.86%) compared to an intestinal type (84/152, 55.26%; P ≤ 0.001), with advanced TNM stages (T3: 44/59, 74.58%; T4:25/32, 78.13%) compared to earlier stages (T1: 25/47, 53.19%; T2: 90/149, 60.40%; P = 0.004), and poorer differentiation grade (poor: 68/90, 75.56%) compared to a higher grade (high: 9/18, 50%, moderate: 74/134, 55.22%) (P = 0.006). Over-expression of PA28β inhibited cell growth, proliferation, and tumorigenicity of MKN-45 GA cells.

Conclusions

These results indicated that PA28β might participate in the origin and progression of GA cancer through changes to cell proliferation activity and tumorigenicity. Therefore, PA28β might be a novel biomarker for GA.

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Aung PP, Oue N, Mitani Y et al (2006) Systematic search for gastric cancer-specific genes based on SAGE data: melanoma inhibitory activity and matrixmetalloproteinase-10 are novel prognostic factors in patients with gastric cancer. Oncogene 25:2546–2557CrossRefPubMed

Bose S, Mason GGF, Rivett AZ (1999) Phosphorylation of proteasomes in mammalian cells. Mol Biol Rep 26:11–14CrossRefPubMed

Cardoso SV, Souza KC, Faria PR, Eisenberg AL, Dias FL, Loyola AM (2009) Assessment of angiogenesis by CD105 antigen in epithelial salivary gland neoplasms with diverse metastatic behavior. BMC Cancer 9:391–398CrossRefPubMed

Ebert M, Yokoyama M, Kobrin MS et al (1994) Induction and expression of amphiregulin in human pancreatic cancer. Cancer Res 54:3959–3962PubMed

Ebert MP, Krüger S, Fogeron ML et al (2005) Overexpression of cathepsin B in gastric cancer identified by proteome analysis. Proteomics 5:1693–1704CrossRefPubMed

Hill CP, Masters EI, Whitby FG (2002) The 11S regulators of 20S proteasome activity Curr. Top Microbiol Immunol 268:73–89

Hoyt MA, Coffino P (2004) Ubiquitin-free routes into the proteasome. CMLS Cell Mol Life Sci 61:1596–1600CrossRef

Huang Q, Yang J, Lin Y et al (2004) Differential regulation of interleukin 1 receptor and Toll-like receptor signaling by MEKK3. Nature Immunol 5:98–103CrossRef

Huang QJ, Huang QL, Chen WN et al (2008) Identification of transgelin as a potential novel biomarker for gastric adenocarcinoma based on proteomics technology. J Cancer Res Clin Oncol 134:1219–1227CrossRefPubMed

Humar B, Fukuzawa R, Blair V et al (2007) Destabilized adhesion in the gastric proliferative zone and c-Src kinase activation mark the development of early diffuse gastric cancer. Cancer Res 67:2480–2489CrossRefPubMed

Ju XZ, Yang JM, Zhou XY, Li ZT, Wu XH (2008) EMMPRIN expression as a prognostic factor in radiotherapy. Clin Cancer Res 12:494–501CrossRef

Kim YS, Burn AL, Goldsmith PK et al (1999) Stable overexpression of MEN1 suppresses tumorigenicity of RAS. Oncogene 18:5936–5942CrossRefPubMed

Kim K, Brush JM, Watson PA et al (2008a) Epidermal growth factor receptor vIII expression in U87 glioblastoma cells alters their proteasome composition, function, and response to irradiation. Mol Cancer Res 6:426–434CrossRefPubMed

Kim JE, Koo KH, Kim YH, Sohn JW, Park YG (2008b) Identification of potential lung cancer biomarkers using an in vitro carcinogenesis model. Experimental and molecular medicine 40:709–720CrossRefPubMed

Kilarski WW, Gerwins P (2009) A new mechanism of blood vessel growth—hope for new treatment strategies. Discov Med 8:23–27PubMed

Krause S, Kuckelkorn U, Do¨rner T, Burmester G-R, Feist E, Kloetzel P-M (2006) Immunoproteasome subunit LMP2 expression is deregulated in Sjögren’s syndrome but not in other autoimmune disorders. Ann Rheum Dis 65:1021–1027CrossRefPubMed

Murata S, Udono H, Tanahashi N et al (2001) Immunoproteasome assembly and antigen presentation in mice lacking both PA28alpha and PA28beta. The EMBO J 20:5898–5907CrossRef

Nonaka T, Nishibashi K, Itoh Y, Yana I, Seiki M (2005) Competitive disruption of the tumor-promoting function of membrane type1 matrix metalloproteinase/matrix metalloproteinase-14 in vivo. Mol Cancer Ther 4:1157–1166CrossRefPubMed

Ossendorp F, Fu N, Camps M et al (2005) Differential expression regulation of the α and β subunits of the PA28 proteasome activator in mature dendritic cells. J Immunol 174:7815–7822PubMed

Perroud B, Lee J, Valkova N et al (2006) Pathway analysis of kidney cancer using proteomics and metabolic profiling. Mol Cancer 5:64–72CrossRefPubMed

Rechsteiner M, Hill CP (2005) Mobilizing the proteolytic machine: cell biological roles of proteasome activators and inhibitors. Trends Cell Biol 15:27–33CrossRefPubMed

Rechsteiner M, Realini C, Ustrell V (2000) The proteasome activator 11 S REG (PA28) and Class I antigen presentation. Biochem J 345:1–315CrossRefPubMed

Roessler M, Rollinger W, Mantovani-Endl L et al (2006) Identification of PSME3 as a novel serum tumor marker for colorectal cancer by combining two-dimensional polyacrylamide gel electrophoresis with a strictly mass spectrometry-based approach for data analysis. Mol Cell Proteomics 5:2092–2101CrossRefPubMed

Stohwasser R, Salzmann U, Giesebrecht J, Kloetzel P-M, HolzhuÈtter H-G (2000) Kinetic evidences for facilitation of peptide channelling by the proteasome activator PA28. Eur J Biochem 267:6221–6230CrossRefPubMed

Tu H, Bonura C, Giannini C et al (2001) Biological impact of natural COOH-terminal deletions of hepatitis B virus X protein in hepatocellular carcinoma tissues. Cancer Res 61:7803–7810PubMed

Voges D, Zwickl P, Baumeister W (1999) The 26S proteasome: a molecular machine designed for controlled proteolysis. Annu Rev Biochem 68:1015–1068CrossRefPubMed

Wilk S, Chen W, Magnusson RP (2000) Properties of the beta subunit of the proteasome activator PA28 (11S REG). Arch Biochem Biophys 384:174–180CrossRefPubMed

Title: Potential roles for PA28β in gastric adenocarcinoma development and diagnosis
Authors: Qiaojia Huang
Qingling Huang
Wansong Lin
Jianyin Lin
Xu Lin
Publication date: 01-08-2010
Publisher: Springer-Verlag
Published in: Journal of Cancer Research and Clinical Oncology / Issue 8/2010
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-010-0778-y

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Potential roles for PA28β in gastric adenocarcinoma development and diagnosis

Abstract

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Methods

Results

Conclusions

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