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CANCER GENOMICS & PROTEOMICS
Volume 2, Number 3, May-June 2005

CONTENTS
PAGE
Immune Signature of Malignant Pleural Mesothelioma as Assessed by Transcriptome Analysis. S. MOHR, A. NEUVILLE, M.C. BOTTIN, J.C. MICILLINO, G. KEITH, B.H. RIHN (Strasbourg; Nancy, France)
125
*Using Comparative Genomics to Leverage Animal Models in the
Identification of Cancer Genes. Examples in Prostate Cancer.
M. W. DATTA, M. A. SUCKOW, S. TWIGGER, M. POLLARD, H. JACOB, P J. TONELLATO(Atlanta, GA; Georgia, Notre Dame, IN; Milwaukee, WI, U.S.A.)
137
Down-regulation of BRMS1 mRNA Expression in Breast Cancer is not Related to the Presence of Axillary Node Metastasis. F. GOMEZ-ESQUER, D. AGUDO, F. MARTINEZ-ARRIBAS, G. DIAZ-GIL, M. POLLAN, J. SCHNEIDER(Madrid, Spain)
145

Proteomic Analysis of Bladder Cancer Cells Reveals Potential Candidates of Biomarkers in Bladder Tumorigenesis. T.-F. WU, H. WU, N.-H. CHOW, C.-F. LIAO, H.-S. LIU (Tainan, Taiwan)

151
 Abstracts of the 1st Int'l Conference of the Hellenic Proteomics Society.
159
   
*Review (page 137)




CANCER GENOMICS & PROTEOMICS 2: 145-150 (2005)


Down-regulation of BRMS1 mRNA Expression in Breast Cancer is not Related to the Presence of Axillary Node Metastasis



F. GÏMEZ-ESQUER1, D. AGUDO1, F. MARTÉNEZ-ARRIBAS2, G. DÉAZ-GIL1, M. POLLÁN 1,3, J. SCHNEIDER1,2


1Universidad Rey Juan Carlos, Facultad de Ciencias de la Salud, Madrid;
2
Fundacion Tejerina-Centro de Patología de la Mama, Madrid;
3
Centro Nacional de Epidemiologia (Epidemiologia del Cáncer), Madrid, Spain



Abstract: Background: BRMS1, recently identified in MDA-MB-435 breast cancer cells, seems to act as a potent antimetastatic gene in experimental tumor models. Materials and Methods: To verify if BRMS1 exerts its action in a similar way in clinical tumors, BRMS1-mRNA expression was investigated in a series of 107 human breast carcinomas and correlated with the presence or not of axillary node metastases. Additionally, BRMS1 expression was correlated with all available clinical (histologic variety, histologic and nuclear grade) and biological parameters (ploidy, expression of Ki67, hormone receptors, c-erb-B2 and p53), as well as with the expression of hMAM- and Nup88-mRNA, previously shown by us to correlate with very low and very high aggressiveness of breast cancer, respectively. Results: Down-regulation of BRMS1 expression in the tumors did not correlate with the presence of axillary node metastases. Furthermore, BRMS1 expression did not correlate with any other of the studied clinical or biological tumor parameters. Conclusion: In clinical breast cancers, down-regulation of BRMS1 expression seems not to mimic the very clear-cut antimetatstatic properties displayed in experimental tumor models.


 
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CANCER GENOMICS & PROTEOMICS 2: 125-136 (2005)


Immune Signature of Malignant Pleural Mesothelioma as Assessed by Transcriptome Analysis



S. MOHR1,3, A. NEUVILLE2, M.C. BOTTIN1, J.C. MICILLINO1, G. KEITH3, B.H. RIHN4


1Institut National de Recherche et de Sécurité, Avenue de Bourgogne, BP27, 54501 Vandoeuvre;
2
Service d'Anatomie Pathologique, CHU de Hautepierre, 67098 Strasbourg;
3
Institut de Biologie Moléculaire et Cellulaire du Centre National de la Recherche Scientifique, UPR 9002, Rue René Descartes, 67084 Strasbourg;
4
INSERM U525, 30 Rue Lionnois, 54000 Nancy, France



Abstract: Malignant pleural mesothelioma (MPM) is a highly malignant tumor arising in patients previously exposed to asbestos fibers. Its increasing incidence and its social, financial and human impact have become a frequent problem in many industrialized countries. The unresponsiveness of malignant mesothelioma to conventional therapies has led clinicians to develop new treatments. As immunotherapy has been shown to offer promising and targeted treatment of MPM patients, the knowledge of the immunoresistance level of MPM may be a valuable tool for "a la carte" therapy. In a previous work, we profiled the gene expression of two MPM tissues compared to healthy mesothelial cells using a 10K cDNA microarray. Subsequent clustering analysis identified several clusters of differentially-expressed genes among those that are functionally-related to the immune system. In this report, we focus on genes with expression changes that may facilitate tumor escape from immune-mediated rejection. We also analyzed the immune reaction by staining the immunocompetent cells surrounding the tumor. Interestingly, the tumor with the strongest escape response, as shown by the expression of numerous immunoresistance-associated genes, displayed the strongest T cell infiltrate. The main genes conferring immunoresistance are CD74, HLADOA, HLADMB, PTGS1, IGFBP7 and TGFB3, by favoring immune tolerance, and CFLAR, DFFA, TNFRSF6, BNIP3L by impairing apoptosis. These observations have fundamental consequences in the understanding of immunological properties of MPM, and offer a new insight into the mechanisms whereby MPM may circumvent host-mediated immune activities and promotes its own development. For an immunomodulation strategy to cure mesothelioma, it is crucial to characterize the MPM "immune signature" to design adapted immunotherapies.


 
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CANCER GENOMICS & PROTEOMICS 2: 151-158 (2005)


Proteomic Analysis of Bladder Cancer Cells Reveals Potential Candidates of Biomarkers in Bladder Tumorigenesis



TING-FENG WU1, HUNG WU1, NAN-HUA CHOW2, CHIN-FENG LIAO2, HSIAO-SHENG LIU3


1Department of Biotechnology, Southern Taiwan University of Technology, Tainan;
2
Department of Pathology and 3Department of Microbiology and Immunology,National Cheng Kung University, Tainan, Taiwan



Abstract: Background: Bladder cancer is the most prevalent type of cancer of the urinary tract in Taiwan. In order to identify the molecular basis of bladder carcinogenesis, we analyzed the proteomic profiling of transitional cell carcinoma (TCC) cell lines to search for novel biomarkers for human bladder cancer. Materials and Methods: Two human TCC cell lines (TSGH8301, Grade II and BFTC905, Grade III) were selected for proteomic analysis. The candidate genes were identified by tandem mass spectrometry. Results: Eight differentially-expressed spots were revealed by high resolution 2-D electrophoresis. Five genes were identified by spectrometry as showing higher expression in the TSGH8301 cells, i.e. heat- shock protein 27, maspin, prohibitin and glutathione S-transferase P1-1 and Chaperonin-containing t-complex polypeptide 1 â subunit. In contrast, S100A4 and annexin V exhibited higher levels in the BFTC905 cells. The differential expression patterns of the identified genes were confirmed by immunoblotting and further analyzed using a variety of TCC cell lines. Conculsion: Our studies implicate the potential role of these de-regulated proteins in bladder cancer and warrant further investigation in clinical samples.


 
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CANCER GENOMICS & PROTEOMICS 2: 137-144 (2005)


Using Comparative Genomics to Leverage Animal Models in the Identification of Cancer Genes. Examples in Prostate Cancer



MILTON W. DATTA1, MARK A. SUCKOW2, SIMON TWIGGER3, MORRIS POLLARD2, HOWARD JACOB3, PETER J. TONELLATO3


1Department of Pathology and Urology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia;
2
Walther Cancer Center, University of Notre Dame, Notre Dame, Indiana;
3
Human and Molecular Genetics Center, Medical College of Wisconsin, Milwaukee, Wisconsin, U.S.A.



Abstract: The identification of cancer biomarkers that will predict susceptibility to disease and subsequent clinical outcome are key components of future genomics-based tailored medical care. Animal models of disease provide a rich resource for the identification of potential cancer biomarkers. Animal models of prostate cancer in particular offer the potential to identify cancer genes associated with dietary and environmental factors. The key issue is the timely and efficient identification of candidate genes that are likely to impact on human prostate cancer. Here, we demonstrate comparative genomics-based methods for the identification of candidate genes in animal models that are associated with human chromosomal regions implicated in prostate cancer. Using publicly available bioinformatics tools, comparisons can be made between cancer-specific datasets, genomic sequencing data and cross-species comparative maps to identify potential cancer biomarkers. This process is demonstrated by using rat models of prostate cancer to identify candidate human prostate cancer genes. Genes identified through these techniques can be screened as biomarkers for response to chemopreventive agents, as well as being used in transgenic or knockout mice to engineer better animal models of human prostate cancer. The bioinformatics techniques outlined here can be used to leverage genomic data from any animal cancer model for use in the study and treatment of human cancer


 
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