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Untitled Document
CANCER GENOMICS & PROTEOMICS
Volume 1, Number
4, July-August 2004
| CONTENTS |
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| Identification of a Novel Transmembrane Protein (UKW): Association with Invasive Status of Mammary Carcinoma Cell Lines and Expression in Pancreatic Carcinoma. S. LOSCH, M. BUCHHOLZ, T. M. GRESS, U. H. WEIDLE (Penzberg; Ulm, Germany) |
263 |
| Amplification of MYCL in Atypical Ewing Tumor. Analysis of Metaphase and Microarray Comparative Genomic Hybridization. T. OZAKI, Y. NAKAGAWA, A. YOSHIDA, K. NUMOTO, S. SUGIHARA, T. KUNISADA, S. HAMAZAKI, H. INOUE (Okayama , Japan) |
275 |
| *Recent Advances in Understanding Carcinogenicity of Oral Squamous Cell Carcinoma: From Basic Molecular Biology to Latest Genomic and Proteomic Findings. R. MEHROTRA, E. N. VASSTRAND, S. O. IBRAHIM (Allahabad, India; Bergen, Norway) |
283 |
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*Colorectal Cancer: Molecular Staging Models that Charactrize Risk and Enhance Prognosis. F. E. AHMED (Greenville, NC, U.S.A.) |
295 |
| Proteomic Determination of Metabolic Protein Expression in Ten Different Tumor Cell Lines. M. GRUBER-OLIPITZ, L. AFJEHI-SADAT, M. FELIZARDO, I. SLAVC, G. LUBEC (Vienna, Austria) |
311 |
| Keratinocyte Growth Factor-Mediated Pattern of Gene Expression in Breast Cancer Cells. X.-P. ZANG, M. L. LERNER, S. V. DO, D. J. BRACKETT, J. T. PENTO (Oklahoma City, Okla,U.S.A.) |
339 |
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| *Review
(pages 283,295) |
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CANCER GENOMICS & PROTEOMICS 1: 263-274 (2004)
Identification of a Novel Transmembrane Protein (UKW): Association with Invasive Status of Mammary Carcinoma Cell Lines and Expression in Pancreatic Carcinoma
STEPHANIE LOSCH1, MALTE BUCHHOLZ2, THOMAS M. GRESS2, ULRICH H. WEIDLE1
1Roche Diagnostics GmbH, Pharma Research, 82377 Penzberg;
2Department of Internal Medicine I, University Hospital, University of Ulm, Robert- Koch-Strasse 8, 89081 Ulm, Germany
Abstract: A novel transmembrane-glycoprotein, referred to as UKW, was identified by expression profiling of a metastatic versus a non-metastatic pancreatic carcinoma cell line (S2-007 and S2-028). UKW is strongly expressed only in the metastatic cell line. The corresponding cDNA encodes for a protein of 374 amino acids. UKW is located on chromosome 11q24.1, a locus which is frequently amplified in pancreatic cancer. Bioinformatic analysis revealed that UKW corresponds to a putative transmembrane-glycoprotein composed of an extracellular domain of 215 aa containing two C2-type Ig folds, a transmembrane region of 23 aa and a highly acidic cytoplasmic region of 117 aa. Sequence alignment revealed homology with human, murine and zebrafish coxsackievirus and adenovirus receptor of 35%, 33% and 36% and colon-related A33 antigen of 32%, respectively. Murine adipose-specific protein 5 (Asp-5), however, exhibited the closest homology (93%), suggesting that UKW represents the human orthologue of Asp-5. Multiple tissue expression array analysis revealed UKW expression in gastrointestinal tissues, brain, aorta and uterus and absence in most other human tissues. In a panel of invasive and non-invasive mammary carcinoma cell lines, relative overexpression of UKW was observed in the invasive cell lines. In addition, increased expression of UKW mRNA was found in pancreatic adenocarcinoma compared to tissues derived from patients with chronic pancreatitis and normal pancreatic tissue.
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CANCER GENOMICS & PROTEOMICS 1: 275-282 (2004)
Amplification of MYCL in Atypical Ewing Tumor. Analysis of Metaphase and Microarray Comparative Genomic Hybridization
TOSHIFUMI OZAKI1, YASUKO NAKAGAWA1, AKI YOSHIDA1, KUNIHIKO NUMOTO1, SHINNSUKE SUGIHARA1, TOSHIYUKI KUNISADA1, SHUJI HAMAZAKI2, HAJIME INOUE1
Science of Functional Recovery and Reconstruction, 1Okayama University Graduate School of Medicine and Dentistry, Okayama;
2Department of Pathology, Okayama University Hospital, Okayama 700-8558, Japan
Abstract: A 20-year-old man developed a soft tissue mass in his right upper arm and, 3 months later, was referred to our hospital. The tumor cells showed brisk mitotic activity and a large amount of cytoplasmic glycogen was demonstrated with periodic acid Schiff stain. A diagnosis of atypical Ewing sarcoma was made. Chemotherapy according to the VACA protocol, comprising vincristine, actinomycin D, cyclophosphamide and doxorubicin was started. The chemotherapy was effective and a limb salvage procedure was performed by implantation of an autoclaved bone after wide tumor excision. During the postoperative chemotherapy, a local recurrence and multiple metastases developed, and the patient died due to disease progression. Fourteen years later, this tumor sample, preserved in a deep-freeze, was analyzed by reverse-transcriptase polymerase chain reaction (RT-PCR) to detect the fusion gene. This tumor had an EWS exon 7 to FLI1 exon 6 fusion transcript. Moreover, metaphase and microarray comparative genomic hybridization (CGH) was done to detect chromosomal instabilities. Many gains and losses were noted on metaphase CGH, and MYCL amplification was identified on microarray CGH.
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CANCER GENOMICS & PROTEOMICS 1: 283-294 (2004)
Recent Advances in Understanding Carcinogenicity of Oral Squamous Cell Carcinoma: From Basic Molecular Biology to Latest Genomic and Proteomic Findings
RAVI MEHROTRA1, ENDRE NORMANN VASSTRAND2, SALAH OSMAN IBRAHIM3
1Department of Pathology, Moti Lal Nehru Medical College, University of Allahabad, 16/2, Lowther Road, Allahabad-211002, India;
2Dental Faculty-Periodontology, University of Bergen, Årstadveien 17, 5009 Bergen;
3Department of Biomedicine, Section of Biochemistry and Molecular Biology, University of Bergen, Jonas Lies Vei 91, 5009 Bergen, Norway
Abstract: The global increase in incidence and mortality, as well as the poor prognosis of oral squamous cell carcinoma (OSCC), has intensified efforts in the field of prevention and early detection of this disfiguring disease. Prevalence of OSCC is common in areas with high consumption of tobacco products and alcohol. Understanding the carcinogenicity of this cancer, using innovative techniques in genomic and proteomic analysis, is the main focus of current research in OSCC, and the hunt for potential molecular biomarkers is accelerating. Although recent advances in preventive, diagnostic and therapeutic techniques related to OSCC have yielded novel molecular targets, partially uncovered signal pathway dominance and advanced early neoplasia detection, the number of deaths attributed to this disease exceeds that reported for cervical cancer, malignant melanoma and Hodgkin's disease. Application of advanced molecular biology techniques for classification, profiling of tumour tissues and/or identification of potential markers of OSCCs is on the rise. This review aims at outlining the available knowledge on epidemiology, aetiology, molecular biology, and genomics and proteomics in relation to OSCCs.
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CANCER GENOMICS & PROTEOMICS 1: 295-310 (2004)
Colorectal Cancer: Molecular Staging Models that Charactrize Risk and Enhance Prognosis
FARID E. AHMED
Department of Radiation Oncology, Leo W. Jenkins Cancer Center, The Brody School of Medicine (BSOM) at East Carolina University (ECU), Greenville, NC, U.S.A.
Abstract: Established staging models for colorectal cancer (CRC) have mostly been based on morphological and clinicopathological criteria, which, while predictive of outcomes at extreme stages (e.g., Dukes' A and D), are less informative at the intermediate stages (e.g., Dukes' B and C). Although this traditional staging has improved survival by adjuvant therapy, a significant percentage of patients develop locoregional recurrences or metastases to the liver and other organs after curative tumor resection. Therefore, it is important to explore the use of new molecular and biological markers, particularly those that provide clues to tumor aggressiveness, in order to target therapeutic outcomes. The clinical usefulness of markers may vary with ethnicity and the anatomical location of the tumor; thus, combinations of markers are needed to develop a "predictive gene expression index" that will identify the underlying potential of the tumor for successful spread to a distant site.
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CANCER GENOMICS & PROTEOMICS 1: 339-344 (2004)
Keratinocyte Growth Factor-Mediated Pattern of Gene Expression in Breast Cancer Cells
XIAO-PING ZANG1, MEGAN L. LERNER2,3, SON V. DO2,
DANIEL J. BRACKETT2,3, J. THOMAS PENTO1
Departments of 1 Pharmaceutical Science, College of Pharmacy and 2Surgery, University of Oklahoma, Health Sciences Center and 3VA Medical Center, Oklahoma City, Oklahoma 73190, U.S.A.
Abstract: Background: Breast cancer metastasis is associated with the motility and invasiveness of breast cancer cells. In a previous study we reported the motility enhancement effect of keratinocyte growth factor (KGF) on breast cancer cells. This study established and characterized the influence of KGF on breast cancer cell motility and determined that KGF-induced motility was observed only in estrogen receptor-positive breast cancer cells. The objective of the present study was to identify genes involved in the KGF motility response in human breast cancer cells. Materials and Methods: Using cDNA expression assays, we compared the expression of mRNA in control and KGF-treated MCF-7 breast cancer cells. Scatter plots and cluster analysis of gene expression were used to determine KGF-mediated gene expression patterns. Results: It was determined that over 100 genes were up- or down-regulated from 3-100 fold at 1h following KGF treatment. We identified up-regulated and down-regulated target genes that are associated with some aspect of tumor progression, proliferation or metastasis. Conclusion: Knowledge of specific genes and patterns of gene regulation associated with KGF-enhanced cell motility may provide important new information concerning the mechanisms involved in tumor metastasis. In addition, these genes and/or protein products may serve as novel therapeutic targets or biomarkers of metastatic progression. The pattern gene of expression observed in this study provides new information on the molecular signature associated with the motility and metastatic progression of breast cancer.
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CANCER GENOMICS & PROTEOMICS 1: 311-338 (2004)
Proteomic Determination of Metabolic Protein Expression in Ten Different Tumor Cell Lines
MARIELLA GRUBER-OLIPITZ, LEILA AFJEHI-SADAT, MAUREEN FELIZARDO, IRENE SLAVC, GERT LUBEC
Department of Pediatrics, Division of Basic Sciences, Medical University of Vienna, Vienna, Austria
Abstract: Alterations in different metabolic pathways are a prerequisite to facilitate malignant features such as invasiveness, metastasis, progression and resistance mechanisms to therapy in tumor cells. To generate metabolic protein expression patterns of tumor cells, and in order to provide an analytical tool for establishing metabolic maps, "metabolomes", we applied two-dimensional electrophoresis (2-DE) followed by mass spectrometry (MALDI-TOF-TOF with LIFT technology) in ten individual tumor cell lines (Saos-2; SK-N-SH; HCT-116; Caov3; A-549; HL60; A-673; A-375; MCF-7; Hela) widely used in tumor research. A series of 124 metabolic proteins, represented by 432 spots, was unambiguously identified by this proteomic approach. The proteins detected comprise a multitude of pathways including intermediary, energy, lipid, nucleic acid, amino acid, carbohydrate, redox, phosphate, iron and folate metabolism. Fifty-six enzymes were present in a single tumor cell line exclusively, whereas only enolase-1, a key component of the glycolytic cascade, was found in all cell lines investigated, thereby underscoring the heterogeneous protein expression profile in different cancer types. Construction of individual protein maps provides an analytical tool and reference base for studying the "metabolome" of tumor cells, forming the basis for designing studies in tumor metabolism, and reveals proteins that can be used as pharmaceutical targets in experimental therapies.
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