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CANCER GENOMICS & PROTEOMICS
Volume 3, Number 6, November-December 2006

CONTENTS
PAGE
New Insights into the Cellular Pathways Affected in Primary Uterine Leiomyosarcoma. S. KAUR, MARCELO L. LARRAMENDY, M. GENTILE,
C. SVARVAR, R. KOIVISTO-KORANDER, H. VAUHKONEN, I. SCHEININ,
A. LEMINEN, R. BÜTZOW, T. BÖHLING, S. KNUUTILA (Helsinki, Finland;
La Plata, Argentina)
347
Proteomic Analysis of the MCF7 Breast Cancer Cell Line. J. HARDOUIN,
L. CANELLE, C. VLIEGHE, J-P. LASSERRE, M. CARON,
R. JOUBERT-CARON (Bobigny Cedex, France)
355
A Comparison of KGF Receptor Expression in Various Types of Human Cancer. X-P. ZANG, MEGAN R. LERNER, STEVEN J. BAHR,
D.J. BRACKETT, J.T PENTO (Oklahoma, OK, USA)
369
Expression Analysis for the Identification of Genes Involved in Acquired Resistance to Cisplatin in Osteosarcoma Cells. K. TAKAZAWA,
H. TSUCHIYA, U. YOSHIMICHI, Y. KANAZAWA, S. II, K. TOMITA
(Kanazawa; Ishikawa, Japan))
373
Resveratrol Regulation of PI3K-AKT Signaling Pathway Genes in MDA-MB-231 Breast Cancer Cells. O.A RACHID, M. ALKHALAF (Safat, Kuwait)
383
Proteomic Studies of Galectin-3 Expression in Human Thyroid Diseases by Immunodetection. P. SUBHASITANONT, C. SRISOMSAP, P. PUNYARIT, J. SVASTI (Bangkok, Thailand)
389




CANCER GENOMICS & PROTEOMICS 3: 347-354 (2006)


New Insights into the Cellular Pathways Affected in Primary Uterine Leiomyosarcoma



SIPPY KAUR1, MARCELO L. LARRAMENDY1,2, MASSIMILIANO GENTILE3, CATARINA SVARVAR1,4, RIITTA KOIVISTO-KORANDER5, HANNA VAUHKONEN1, ILARI SCHEININ1,3, ARTO LEMINEN5, RALF BUTZOW1, TOM BOHLING1, SAKARI KNUUTILA1



1Department of Pathology, Haartman Institute and HUSLAB, University of Helsinki and Helsinki University Central Hospital, P.O.B. 21, FI-00014 Helsinki, Finland;
2Laboratorio de Citogenetica y Catedra de Citologia, Facultad de Ciencias Naturales y Museo, Universidad Nacional de La Plata, 1900 La Plata, Argentina;
3Biomedicum Bioinformatics Unit, Haartmaninkatu 8, FI-00290 Helsinki, Finland;
4Department of Plastic Surgery and 5Department of Gynecology,
Helsinki University Central Hospital, P.O.B. 340, FI-00029 HUS, Helsinki, Finland



Abstract: Resistance to chemotherapeutic agents and radiotherapy has kept surgery the primary treatment of uterine leiomyosarcoma (ULMS). In search of leads for potential therapeutic targets, array CGH (aCGH) was used to obtain a genomewide pattern of ULMS-specific genetic imbalances and to define the affected biological processes. Fine-resolution genomewide aCGH analysis was performed using customised 16K cDNA microarrays on 18 primary ULMS cases. Furthermore, patterns of DNA copy number changes were assessed for associations with clinical parameters, i.e., tumour grade, tumour size and patient status at last follow-up. Our aCGH results demonstrated extensive DNA copy number changes in all chromosomes. Of the 10,590 gene loci included in the analysis, 4,387 were found to be affected by DNA copy number gains and 4,518 by DNA copy number losses in at least one case. Further analyses revealed that 231 of these were commonly gained, and 265 lost in at least 20% of the cases. The gains affected loci at 1p, 1q, 2p, 3p, 6p, 8q, 10q and 18q, whereas losses were observed at 2q, 4q, 6p, 6q, 7p, 7q, 13q, 14p, 16q, 19p, Xp and Xq. Enrichment analysis of biological processes revealed the gained genes to be involved in the G1/S transition of mitotic cell cycle, co-translational protein targeting to membrane, actin filament polymerisation and positive regulation of cytokine biosynthesis, whereas the genes affected by losses were associated with DNA replication, chromatin modification, telomere maintenance, meiosis, mitosis and angiogenesis. These biological processes featured prominently two well-established tumour suppressors (BRCA2, EREG) and one proto-oncogene (GFI1). No statistically significant associations were found between the aberration patterns and clinical variables. Analysis of gene pathways using aCGH uncovered the biological networks involved in malignant progression of ULMS.


 
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CANCER GENOMICS & PROTEOMICS 3: 355-368 (2006)


Proteomic Analysis of the MCF7 Breast Cancer Cell Line



JULIE HARDOUIN, LUDOVIC CANELLE, CELINE VLIEGHE,
JEAN-PAUL LASSERRE, MICHEL CARON, 
RAYMONDE JOUBERT-CARON



Laboratory of Protein Biochemistry and Proteomics, UMR CNRS 7033 (BioMoCeTi), UFR SMBH, Paris13 University, 93017 Bobigny Cedex, France



Abstract: Background: The MCF7 breast cancer cell line is a cellular model for breast cancer studies and marker discovery. Therefore, a better knowledge of its proteome is a prerequisite for a more efficient use of this model. Materials and Methods: Proteins expressed during the exponential growth phase of MCF7 cells were analyzed and mapped using two-dimensional gel electrophoresis and mass spectrometry. Results: From the spots excised from preparative gels of whole-cell extracts, a subset of 368 different polypeptides, corresponding to 249 different proteins, was identified. These polypeptides were positioned on a silver-stained gel to construct a reference map. Conclusion: The data allowed the construction of the most extensive reference map for MCF7 published to date, with 189 novel proteins, which had not been previously listed on maps, and are now accessible on World 2D-PAGE database, providing a basis for further studies on MCF7.


 
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CANCER GENOMICS & PROTEOMICS 3: 369-372 (2006)


A Comparison of KGF Receptor Expression in Various Types of Human Cancer



XIAO-PING ZANG1, MEGAN R. LERNER2,3, STEVEN J. BAHR1,
DANIEL J. BRACKETT2,3, J. THOMAS PENTO1



Departments of 1Pharmaceutical Sciences and 2Surgery, University of Oklahoma Health Sciences Center;
3VA Medical Center, Oklahoma City, Oklahoma 73190, OK, U.S.A.



Abstract: Background: Keratinocyte growth factor (KGF) has been observed to produce a rapid increase in the motility of breast cancer cells. KGF/KGFR (KGF receptor) signaling has also been demonstrated in the progression of many types of human cancer. The objective of the present study was to compare KGFR expression in various types of cancer. Materials and Methods: A cancer profiling array containing cDNA from 154 tumor and paired normal samples representing 19 types of human cancer was employed. Results: The results of the present study indicate that KGFR expression is enhanced in many types of human carcinomas at an early stage of cancer development, suggesting that KGFR overexpression may be an early signal in the progression of these cancers. However, the stage of cancer progression and relative level of expression varied considerably among the various types of cancer. Conclusion: These findings suggest that tumor KGFR levels may serve as a prognostic biomarker for cancer staging and/or treatment.


 
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CANCER GENOMICS & PROTEOMICS 3: 373-382 (2006)


Expression Analysis for the Identification of Genes Involvedin Acquired Resistance to Cisplatin in Osteosarcoma Cells



KOUTAROU TAKAZAWA1, HIROYUKI TSUCHIYA1, UEDA YOSHIMICHI2, YOSHIMITSU KANAZAWA1, SADAO II1,
KATSURO TOMITA1



1Department of Orthopaedic Surgery, Graduate School of Medical Science,
Kanazawa University, 13-1 Takara-machi, Kanazawa;
2Department of Pathology, Kanazawa Medical University,
1-1 Uchidana-machi, Kahoku-gun, Ishikawa, Japan



Abstract: Background: Clinical observations indicate that tumour cells can acquire tolerance when an anticancer drug is administered repeatedly. In the present study, the gene expression in cisplatin-resistant cells was analysed to identify early changes in gene expression in the course of cisplatin exposure. Materials and Methods: After establishing a cisplatin-resistant human osteosarcoma subline (OST/R) and two additional sublines by more brief repeated exposure, cDNA expression microarrays were used to study genes linked with prolonged exposure to cisplatin of human cancer cells. Results: OST/R cells showed increased expression of 17 genes and reduced expression of 14. Genes associated with DNA repair, apoptosis, cell cycle progression, and proliferation were associated with the acquired resistance. Genes showing early changes were also identified. Conclusion: Identification of genes showing altered expression in the early stages of development of resistance to cisplatin may help to improve the therapeutic effectiveness of this drug.


 
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CANCER GENOMICS & PROTEOMICS 3: 383-388 (2006)


Resveratrol Regulation of PI3K-AKT Signaling Pathway Genes in MDA-MB-231 Breast Cancer Cells



OUSAMA RACHID, MOUSSA ALKHALAF



Department of Biochemistry, Faculty of Medicine, Kuwait University, Safat, Kuwait



Abstract: Background: Resveratrol (RSVL), a natural compound found in grapes and other food products, has been described to exert cancer chemopreventive activities. However, the cellular and molecular basis of its anticancer activity is largely undefined. The aim of the present study was to identify RSVL target genes in the MDA-MB-231 breast cancer cell line using cDNA arrays representing genes of the PI3K/AKT signaling pathway. Materials and Methods: Total RNA from control and RSVL-treated cells was used to synthesize biotinylated cDNA probes. cDNA arrays were hybridized with the probes and signals were detected with a chemiluminescent method. Western blotting analysis was used to validate the arrays' gene expression. Results: At the cDNA level, 13 genes were altered (at least 2-fold difference) by RSVL treatment. At the protein level, both c-fos and P70S6K were also regulated. Conclusion: Using gene arrays it was shown for the first time that c-fos and p70S6 kinase were regulated by RSVL.


 
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CANCER GENOMICS & PROTEOMICS 3: 389-394 (2006)


Proteomic Studies of Galectin-3 Expression in Human Thyroid Diseases by Immunodetection



PANTIPA SUBHASITANONT1, CHANTRAGAN SRISOMSAP1,
PHAIBUL PUNYARIT2, JISNUSON SVASTI1,3



1Laboratory of Biochemistry, Chulabhorn Research Institute;
2Department of Pathology, Pramongkutklao College of Medicine;
3Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok, Thailand



Abstract: Galectin-3 expression in thyroid diseases was studied by 1-DE immunoblotting. Expression was markedly elevated in thyroid papillary carcinoma, compared to follicular adenoma, follicular carcinoma or non-neoplastic diseases. Galectin-3 expression was also elevated in malignant cancers of bone, breast, colon, esophagus, larynx, lung and ovary. Four cases of thyroid papillary carcinoma with metastasis gave 2-3 bands on 1-DE immunoblotting. 2-DE immunoblotting of gelectin-3 showed 3 dark spots with MW/pI 32.9/8.29, 31.0/8.40 and 30.0/8.40 and 2 light spots.


 
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