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Untitled Document
CANCER GENOMICS & PROTEOMICS
Volume 4, Number
5, September-October 2007
| CONTENTS |
PAGE |
| * Collagen – A Necessary Accomplice in the Metastatic Process. P.S. NERENBERG, R. SALSAS-ESCAT, C.M. STULTZ (Cambridge, MA, U.S.A.) |
319 |
| Differential Expression of Ribosomal Proteins in a Human Metastasis Model Identified by Coupling 2-D Liquid Chromatography and Mass Spectrometry. P. KREUNIN, C. YOO, V. URQUIDI, D.M. LUBMAN, S.GOODISON (Michigan; Ann Arbor, MI; Jacksonville, FL, U.S.A.) |
329 |
| 17HSD 2 may be Higher in African-American Breast Cancer and is Associated with Estrogen Receptor-negative Tumors.r. R. YAEGER, P.C. NOLAN, T. SU, A. AVILA-BRONT, X. WANG, Y.-K. K. CHEUNG, H. LIU, V.S. RANGARAJAN, H. HIBSHOOSH, C.A. POWELL, A.K. JOE (New York, NY, U.S.A.) |
341 |
| *Molecular Profiling for the Identification of New Biomarkers in Smokers and Cancer Patients. K.ALBERMANN, S. LANG, R. ZEIDLER (Essen; Munich, Germany) |
349 |
Genome-wide Expression Profiling Reveals New Insights into Pathogenesis and Progression of Testicular Germ Cell Tumors. K. BIERMANN, L.S.C. HEUKAMP, K. STEGER, H. ZHOU, F.E. FRANKE, V. SONNACK,
R. BREHM, J. BERG, P.J. BASTIAN, S.C. MÜLLER, L. WANG-ECKERT, R. BUETTNER (Bonn; Giessen; Cologne, Germany) |
359 |
Activity of the Glutathione Peroxidase-2. Differences in the Selenium-dependent Expression between Colon and Small Intestine. J. BARTEL, T. BARTZ, C. WOLF, E. CHARKIEWICZ, M. KÜHBACHER, T. POHL, A.
KYRIAKOPOULOS (Berlin; Teltow, Germany) |
369 |
*Review
CANCER GENOMICS & PROTEOMICS 4: 319-328 (2007)
Collagen - A Necessary Accomplice in the Metastatic Process
PAUL S. NERENBERG, RAMON SALSAS-ESCAT, COLLIN M. STULTZ
Harvard-MIT Division of Health Sciences and Technology and Department of Electrical Engineering and Computer Science Massachusetts Institute of Technology, U.S.A.
Abstract: The prognosis for cancer patients with metastatic disease remains poor. For cancer to metastasize from a primary tumor to distinct sites in the body, both the extracellular matrix and basement membrane - physiological barriers whose primary structural constituent is collagen - must be degraded to allow the passage of tumor cells. Collagen has long been assumed to be a passive background upon which the biochemical events of metastasis take place, but recent experimental developments instead point to a novel active role for collagen in the immune response to metastasis. Along with a new hypothesis for the mechanism of collagen degradation, these data suggest innovative approaches to prevent the spread of cancer from the primary tumor site.
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CANCER GENOMICS & PROTEOMICS 4: 329-340 (2007)
Differential Expression of Ribosomal Proteins in a Human Metastasis Model Identified by Coupling 2-D Liquid Chromatography and Mass Spectrometry
PAWEENA KREUNIN1*, CHUL YOO1*, VIRGINIA URQUIDI2, DAVID M. LUBMAN1,3,4, STEVE GOODISON5
1Department of Chemistry, University of Michigan, Ann Arbor, MI;
2Department of Medicine and 5Department of Surgery, University of Florida,
Jacksonville, FL;
3Department of Surgery, University of Michigan Medical School,
Ann Arbor, MI;
4Comprehensive Cancer Center, University of Michigan Medical Center,
Ann Arbor, MI, U.S.A.
Abstract: Background: Proteomic profiling of an experimental tumor metastasis model has the potential to identify gene products that can influence this fatal phenotype of tumor cells. In this study, we focused on the notoriously difficult to assess ribosomal protein component of a pair of cell lines which originate from the same tumor but have opposite metastatic capabilities. Materials and Methods: Cell lysate proteins were separated using a two-dimensional liquid chromatographic system directly coupled to an ESI-TOF mass spectrometer for accurate intact protein MW analysis. Characterization of distinct post-translational modifications and sequence variation within several ribosomal proteins was obtained using monolithic capillary LC/MS/MS, MALDI-MS and -MS/MS. Results: The combination of these techniques enabled the identification of 45 unique ribosomal proteins, several of which were differentially expressed in metastatic M4A4 cells. Conclusion: The described proteomic profiling approach enables the identification of phenotype-associated ribosomal proteins for subsequent functional analyses and disease biomarker development.
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CANCER GENOMICS & PROTEOMICS 4: 341-348 (2007)
17HSD 2 may be Higher in African-American Breast Cancer and is Associated with Estrogen Receptor-negative Tumors
RONA YAEGER1, PATRICIA C. NOLAN1, TAO SU2, ALEXA AVILA-BRONT1,
XIAOMEI WANG2, YING KUEN K. CHEUNG2,3, HUI LIU1, VIBHAV S. RANGARAJAN1,
HANINA HIBSHOOSH2,4, CHARLES A. POWELL1,2, ANDREW K. JOE1,2
1Department of Medicine, 2Herbert Irving Comprehensive Cancer Center,
3Department of Biostatistics, and 4Department of Pathology,
Columbia University Medical Center, New York, NY 10032, U.S.A..
Abstract: Background: African-American women develop more aggressive breast cancers and at an earlier age compared with Caucasian women. Materials and Methods: We compared gene expression profiles of breast cancer cell lines that were developed from African-American and Caucasian patients to identify biological differences in breast cancers that develop in these groups. Real-time PCR was used to evaluate mRNA expression in cell lines and in a series of breast cancer cases. Gene microarray signal intensities were also analyzed in the International Genomics Consortium Expression Project for Oncology (expO) dataset. Results: 17,-Hydroxysteroid dehydrogenase type 2 (17HSD 2) gene and mRNA expression were significantly higher in the African-American cell lines (p<0.05). However, 17HSD 2 expression did not differ significantly between the two cohorts in either our clinical series or the expO dataset. 17HSD 2 expression was found to be predictive of younger age at diagnosis and estrogen receptor status. Conclusion: Overexpression of 17HSD 2 in African-American breast cancer may contribute to the increased proportion of estrogen receptor-negative breast cancers and worse clinical outcome among African-American patients.
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CANCER GENOMICS & PROTEOMICS 4: 349-358 (2007)
Molecular Profiling for the Identification of New Biomarkers in Smokers and Cancer Patients
KAJ ALBERMANN1, STEPHAN LANG2, REINHARD ZEIDLER3
1Biomax Informatics AG, D-82152 Martinsried,
2University of Essen, ENT-Department, D-45122 Essen,
3University of Munich, ENT-Department, D-81377 Munich, Germany.
Abstract: Smoking is associated with different serious diseases, including cancer. The fact that only a minority of smokers develops tobacco-associated diseases suggests the contribution of other individual factors, which are still far from understood. New technologies that can be referred to as 'molecular profiling' allow for investigating the deregulation of thousands of genes simultaneously. Numerous such studies have investigated in vitro and in vivo the effects of smoking in different cell types aiming at a better understanding of smoking-induced diseases and the detection of new biomarkers of exposure and harm. This review is a short survey of these investigations and how they have contributed to the detection of new biomarkers and to a better understanding of smoking-induced harm.
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CANCER GENOMICS & PROTEOMICS 4: 369-372 (2007)
Activity of the Glutathione Peroxidase-2. Differences in the Selenium-dependent Expression between Colon and Small Intestine
JURGEN BARTEL1, TORSTEN BARTZ1, CHRISTIAN WOLF1,
ELZBIETA CHARKIEWICZ1, MARKUS KUHBACHER1, THOMAS POHL2, ANTONIOS KYRIAKOPOULOS1
1Department of Molecular Trace Element Research in the Life Sciences,
Hahn-Meitner-Institut, Berlin; 2WITA GmbH, Teltow, Germany .
Abstract: Background: Selenium (Se) is an essential element which is involved in various biological processes in nearly all tissues of animals and human, e.g. protection against oxidative stress in the cardiovascular system, and may play a role in cancer protection. It is incorporated in the proteome in the form of the genetically encoded amino acid selenocysteine, which is the characteristic component of the selenoproteins. Materials and Methods: We investigated the expression of the selenoenzyme GPx-2 which is predominantly present in the tissues of the gastrointestinal tract such as the small intestine and therefore named gastrointestinal glutathione peroxidase. Rats were fed with a Se-adequate or Se-deficient diet and GPx2 was assessed by means of enzyme activity with respect to the Se concentration in tissues of the colon and small intestine. Se quantification was carried out by means of graphite furnace atom absorption spectrometry and 2D-gel electrophoresis was applied to investigate the expression of the proteins of the small intestine tissue samples. Results: Twenty-eight differences could be distinguished in the protein spot distribution of the 2D-gels of the homogenates. The GPx-2 activity in the Se-deficient rat colon samples was 6.8 fold lower than in the Se-adequate rats in contrast to 1.2 fold lower levels between the corresponding samples in the small intestine. Conclusion: This finding might explain the different susceptibility of the colon and the small intestine to cancer and support the theory of the protective effect of selenium in the gastrointestinal tract.
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CANCER GENOMICS & PROTEOMICS 4: 359-368 (2007)
Genome-wide Expression Profiling Reveals New Insights into Pathogenesis and Progression of Testicular Germ Cell Tumors
KATHARINA BIERMANN1*, LUKAS CARL HEUKAMP1*, KLAUS STEGER2, HUI ZHOU1, FOLKER ERNST FRANKE3, VIOLETTA SONNACK2, RALPH BREHM4, JOHANNES BERG5, PATRICK JAN BASTIAN6, STEFAN CAJETAN MULLER6, LIHUA WANG-ECKERT7, REINHARD BUETTNER1
1Department of Pathology and 6Department of Urology, University of Bonn;
2Department of Urology and Pediatric Urology;
3Department of Pathology, and 4Institute of Veterinary-Anatomy, -Histology and -Embryology, University of Giessen;
5Institute of Theoretical Physics, University of Cologne;
7Laboratory for Experimental Psychiatry, Life & Brain Center, Bonn, Germany.
Abstract: Testicular germ cell tumors (GCT) are the most frequent malignancy in young adults and arise from intratubular germ cell neoplasia undetermined (IGCNU, also referred to as carcinoma in situ, CIS). To determine the transcriptional programs involved in the transition from normal germ cells to GCT, and to further elucidate genetic differences between seminomas and non-seminomatous GCT the global expression profile of 12 neoplastic and 3 normal testicular tissues were investigated by whole genome cDNA microarrays. Transcriptional differences between seminomas and embryonal carcinomas were determined and gene signatures characterizing histological subtypes of GCT were identified. The most significant difference between seminomas and embryonal carcinomas was the expression of spermatogenesis-associated genes (PRAME, MAGEA4, SPAG1, HPX) in seminomas and regulatory genes DNMT3B and SOX2 as well as small molecular weight keratins KRT8, KRT18 in embryonal carcinomas. The expression of several selected genes (CK18, MAGE-A4, SOX2, DNMT3B, CD30, KIT) was studied by immunohistochemistry or reverse transcriptase-polymerase chain reaction (RT-PCR) in a large collective of GCT. In summary, our data identified tumor type-specific gene signatures of GCT and provided new insights into genetic pathways driving the transition to seminomas and embryonal carcinomas from their respective precursor lesions.
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