|
Untitled Document
CANCER GENOMICS & PROTEOMICS
Volume 2, Number
4, July-August 2005
| CONTENTS |
PAGE |
| Proteomic
Analysis of Membrane-associated Proteins from the Breast Cancer Cell Line
MCF7. C. PIONNEAU, L. CANELLE, J. BOUSQUET, J. HARDOUIN, J. BIGEARD,
M. CARON, R. JOUBERT-CARON (Bobigny, Marcy l'Etoile, France) |
199 |
| Specific Expression
of Potential Tumour Marker Proteins, Similar to No On or Off Transient A
and HIRA-interacting Protein 5, in Mouse N1E-115 Neuroblastoma Cell Line.
J-E. OH, E. ENGIDAWORK, J.-H. SHIN, G. LUBEC (Vienna,
Austria; Addis Ababa, Ethiopia) |
209 |
| Biomarkers
for Sensitivity to Docetaxel and Paclitaxel in Human Tumor Cell Lines In
Vitro. E. IZBICKA, D. CAMPOS, G. CARRIZALES,
A. TOLCHER (San Antonio,TX, USA) |
219 |
| *Stathmin
in Cell Proliferation and Cancer Progression. G.V. SHERBET, F.
CAJONE (Newcastle-upon-Tyne, U.K.; Huntington Beach, CA, U.S.A.; Milan,
Italy) |
227 |
| The
Cell Cycle Regulators P16INK4a,
P15INK4b and Cyclin D1: Relationship
to Clinicopathological Parameters and Disease-free Survival in Laryngeal
Carcinoma Patients.E.
EL-SALAHY, A. H. ABOU-GHALIA, A. ADLI, S. K. KASSIM (Cairo,
Egypt) |
239 |
| *Tumor Suppressor
Genes on Human Chromosome 3 and Cancer Pathogenesis. S. INGVARSSON
(Reykjavik, Iceland) |
247 |
| |
|
| *Reviews
(pages 227,247) |
|
CANCER GENOMICS & PROTEOMICS 2: 239-246 (2005)
The Cell Cycle Regulators P16INKa, P15INK4b and Cyclin D1: Relationship to Clinicopathological Parameters and Disease-free Survival in Laryngeal Carcinoma Patients
EMAN EL-SALAHY1, AZZA H. ABOU-GHALIA1, AHMED ADLI2, SAMAR K. KASSIM1
1Medical Biochemistry and 2Otolaryngology Departments, Faculty of Medicine, Ain Shams University, Cairo, Egypt
Abstract: Laryngeal squamous cell carcinoma (LSCC) is a frequent malignancy with a complex and undefined etiology to date. The recently identified cyclin-dependent kinase inhibitor p15INK4b is frequently deleted in human tumors. Previous evidence has pointed to a related gene, p16INK4a, as another target for deletion. Both genes express cyclin D inhibitor proteins. To determine the importance of cell cycle regulators in LSCC relative to more traditional surgical and pathological prognostic factors, p15INK4b, p16INK4a and cyclin D1 analyses were performed. Forty-one malignant tumor tissues and 20 minimal pathological lesions (MPL) of the larynx were examined for deletion of the p16INK4a and p15INK4b genes using polymerase chain reaction. Cyclin D1 expression was studied by Western blotting. Deletions of p16INK4a and p15INK4b were observed in 48.8 % and 51.2% of LSCC patients, respectively. Meanwhile, no deletion was observed in MPL (p<0.001). Cyclin D1 was expressed in 43.9% of patients with LSCC versus 30% with MPL (p=0.29). Although the frequency of p16INK4a and p15INK4b deletions were higher in advanced than early tumor stages, the difference was statistically insignificant. Ninety percent of patients with deletion of p16INK4a had deletion of the p15INK4b gene. Both cyclin D1 expression and deletion of p15INK4b were found to be independent prognotic predictors of disease recurrence. p16INK4a and p15INK4b gene deletions are exclusively related to malignancy of the larynx. Cyclin D1 expression and p15INK4b gene deletion are potential prognostic indicators of recurrence of LSCC.
|
CANCER GENOMICS & PROTEOMICS 2: 209-218 (2005)
Specific Expression of Potential Tumour Marker Proteins, Similar to No On or Off Transient A and HIRA-interacting Protein 5, in Mouse N1E-115 Neuroblastoma Cell Line
JI-EUN OH1, EPHREM ENGIDAWORK2, JOO-HO SHIN1, GERT LUBEC1
1Department of Paediatrics, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria;
2Department of Pharmacology, School of Pharmacy, Addis Ababa University, P.O.Box 1176, Addis Ababa, Ethiopia
Abstract: Background: Improved cancer detection involving suitable biomarkers with easy applicability is a challenge in our fight against cancer. Biomarkers that provide significant insight into the behaviour of neuroblastoma would greatly aid in identifying patients at risk of disease progression, those whose disease has progressed sub-clinically and those who would benefit from currently available systemic therapies. Materials and Methods: Matrix-assisted laser desorption and ionization-time-of-flight (MALDI-TOF-TOF) is an evolving proteomic technology for improving biomarker discovery, that allows for rapid and sensitive analysis of complex protein mixtures generated from body fluids, cells and/or tissues. MALDI-based profiling identifies unique, differentially-expressed proteins relating to specific cancer-related disease states. A proteomic map of the murine neuroblastoma N1E-115 cell line was generated and MALDI-TOF-TOF utilized in a search for tumour marker candidates. Results: The analytical tool identified and characterized similar to no on or off transient A [fragment] and HIRA-interacting protein 5 proteins that have never been described in any normal or tumour cell lines. Conclusion: These findings suggest that the proteins may serve as candidate markers for screening, staging and drug selection for the management of neuroblastoma, owing to their tumour-specific expression.
|
CANCER GENOMICS & PROTEOMICS 2: 247-254 (2005)
Tumor Suppressor Genes on Human Chromosome 3 and Cancer Pathogenesis
SIGURDUR INGVARSSON
Institute for Experimental Pathology, University of Iceland at Keldur, 112-Reykjavik, Iceland
Abstract: The short arm of chromosome 3 is frequently altered in human cancers of different tissue origin. Certain regions on the chromosome arm 3p have been defined by deletion studies in human cancer cells and tissues. Also, regions at 3p are eliminated in microcell hybrids parallel to increased tumorigenicity in immunosuppressed mice. We have analysed chromosome instability and several genes involved in tumor pathogenesis at 3p, such as VHL, RIITGFB, CATNB, MLH1 and FHIT. By studying eleven tumor types, we have shown that the importance of CER1 (common eliminated region 1) transgresses tissue specificity. Comparative studies on losses of VHL, FHIT/FRA3B and CER1 show that the CER1 region is preferably lost in human tumors. Alterations of FHIT are associated with reduced survival of breast and colon cancer patients. The FHIT gene is located at the constitutive fragile region, FRA3B. Chromosome 3, particularly FHIT, is unstable in breast cancer patients who have germ line mutation in the BRCA2 gene. The chromosome instability in BRCA2 tumors reflects the DNA repair mechanism of the gene product Brca2. It can be concluded that our results reflect a synergism of tumor suppressor gene (TSG) losses at the chromosome 3p region in relation to the biological behavior of tumor cells and tumor pathogenesis.
|
CANCER GENOMICS & PROTEOMICS 2: 227-238 (2005)
Stathmin in Cell Proliferation and Cancer Progression
G.V. SHERBET1,2, F. CAJONE3
1School of Electrical and Electronic Engineering, University of Newcastle-upon-Tyne, U.K.;
2Institute for Molecular Medicine, Huntington Beach, CA, U.S.A.;
3Department of Biomedical Science and Technology, School of Medicine, University of Milan, Segrate, Italy
Abstract: The phosphoprotein stathmin exerts profound influences on cell proliferation, differentiation and in cell motility. These phenotypic features are displayed in response to specific signals imparted to the cell by biological response modifiers. Stathmin functions as a focal point in co-ordinating and directing the cellular signals into specific and defined pathways. Two biological features that characterise cancer are the deregulation of cell proliferation leading to tumour growth and invasive behaviour. Stathmin is up-regulated in many neoplasms and the modulation of its expression correlates with invasion and metastasis and highly proliferating normal tissues. The integrity of the transduction of extracellular signals is essential for the normal functioning of the cellular machinery in cell differentiation, morphogenesis and cell proliferation, apoptosis, growth and senescence. Stathmin mediates these pathways of signalling. Stathmin has been implicated in both G1-S and G2-M checkpoint control of cell cycle progression by influencing the dynamics of microtubule formation and progression of the cell cycle. Stathmin appears to exert its regulatory effects at both G1-S and G2-M checkpoints by interacting with other cell cycle control proteins such as p53 and rb and with cancer metastasis promoting or inhibiting genes as well as other proteins such as heat shock proteins. Stathmin co-ordinates the signalling by extracellular matrix proteins, and defines intercellular adhesion and cell motility. Therefore, the deregulation of stathmin function would have profound implications in the pathogenesis and progression of cancer.
|
CANCER GENOMICS & PROTEOMICS 2: 199-208 (2005)
Proteomic Analysis of Membrane-associated Proteins from the Breast Cancer Cell Line MCF7
C. PIONNEAU1,2, L. CANELLE1, J. BOUSQUET1, J. HARDOUIN1, J. BIGEARD, M. CARON1, R. JOUBERT-CARON1
1Protein Biochemistry and Proteomics Laboratory (LBPP), UFR SMBH, Universite Paris 13, 93017 Bobigny;
2 R&D Immunoessais et Proteomique, bioMerieux, Chemin de l’Orme, 69280 Marcy l’Etoile, France
Abstract: Background: Proteins associated with cancer cell membranes represent targets of choice for humoral immune response as well as potential tumour marker proteins in human malignancies. However, proteomic analysis of these proteins, and more generally of low-soluble proteins, remains difficult. Materials and Methods: The breast cancer cell line MCF7 was selected to evaluate a sequential extraction method that enables simple fractionation of human cell proteins according to their subcellular localization, yielding subproteomes enriched in cytosolic and membrane-associated proteins, respectively. A crude plasma membrane preparation was followed by the solubilisation of proteins using trifluoroethanol (TFE) as co-solvent. Results: Cross-matching and statistical analysis performed for each set of two-dimensional electrophoresis (whole-cell, membrane and soluble extracts) and between the different sets highlighted the reproducibility of the extraction process and its usefulness for proteomic analysis. Eighty-three % of the spots of the gels corresponding to the membrane fraction were not found in the gels of the soluble fraction. Conclusion: Due to its simplicity, the approach described here appears well suited for membrane proteomic investigation of human cancer cells and detection of potential biomarkers undetected by current techniques.
|
CANCER GENOMICS & PROTEOMICS 2: 219-226 (2005)
Biomarkers for Sensitivity to Docetaxel and Paclitaxel in Human Tumor Cell Lines In Vitro
ELZBIETA IZBICKA, DAVID CAMPOS, GILBERT CARRIZALES, ANTHONY TOLCHER
Cancer Therapy and Research Center, The Institute for Drug Development,14960 Omicron Drive, San Antonio, TX 78245, U.S.A.
Abstract: Background: Paclitaxel and docetaxel affect microtubule polymerization, yet surprising differences in tumor sensitivity to the taxanes have been observed. Docetaxel was superior to paclitaxel in inhibiting in vivo growth of human lung and prostate but not breast cancer models. Materials and Methods: We compared drug cytotoxicity, effects on â-tubulin isoforms, markers of apoptosis and proteomic profiles in human prostate (LNCaP), lung (SK-MES, MV-522) and breast (MCF-7, MDA-231) cancer cell lines in vitro. Results: Cytotoxicity followed the order SK-MES
|
|
|
|
