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133 Expression of the PDGF B- (c-cis) and PDGF A-chain genes and the PDGF B-type receptor in human malignant mesothelioma cell lines
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Abstracts 132
M A L I G N A N T PLEURAL MESOTHELIOMA: C H R O M O S O M E A N D D N A ANALYSIS. M. TiainenL L. Tammilehto 2,K. Mattson 2,~.Kere I,and S. Knuutila~.IDepartment of Medical Genetics,University of Helsinki, and 2Department of Pulmonary Medicine, Helsinki University Central Hospital, Helsinki, Finland.
Successful cytogenetic studies were performed on tumor and/or pleural fluid samples from 34 out of 38 patients with malignant pleural mesothelioma. Clonal chromosome abnormalities were detected in 25 patients, 19 of them studied before treatment. Most of the karyotypic findings were complex including several structural and numerical aberrations, and no single abnormality common to all 25 patients was seen. Chromosomes most frequently involved in abnormalities were 1, 3, 7, 9,11,14 and 22. Partial or total polysomies of #7 (13 patients) and #11 (11 patients) and partial or total monosomies of @3 (12 patients), @9 (12 patients), #14 (11 patients) and #22 (14 patients) as well as translocations and deletions involving bands lp11-22 (11 patients) seem to be nonrandom abnormalities in mesothelioma. Based on the cytogenetic findings the study has been carried on to molecular level. Southern blot hybridization analyses have been performed on DNA samples from tumors of 26 patients. The following chromosome 7 genes have thus far been screened for rearrangements and amplifications: MET oncogene, multiple drug resistance gene, epidermal growth factor receptor gene (ERB-B oncogene), platelet derived growth factor gene, and plasminogen activator inhibitor gene. Instances of gene amplifications have been seen.
133
EXPRESSION OF THE PDGF B- (C-SIS} A N D PDGF A-CHAIN GENES A N D THE PDGF B-TYPE RECEPTOR IN H U M A N M A L I G N A N T M E S O T H E L I O M A CELL LINES. M. A. VersnelI,M. J.Bouts I, H. C. Hoogsteden 2,Th. H. van der Kwast 3,and A. Hagemeijer ~.~Department of Cell Biology, Immunology and Genetics, 2Department of Pulmonary Diseases, 3Department of Pathology, Erasmus University and Academic Hospital Dijkzigt,Rotterdam, The Netherlands.
Malignant mesotheliomas are mesodermally derived tumors. In a panel of malignant mesothelioma cell lines from patients with a confirmed malignant mesothelioma we studied the expression of the PDGF B-(c-sis) and PDGF A-chain genes. Cultured normal mesotheliai cells were used as a control. The malignant mesothelioma cell lines clearly expressed the 4.0 kb c-sis mRNA while the normal mesothelial cell lines did not express this messenger. The PDGF A-chain expression was only slightly elevated in the malignant mesothelioma cell lines compared to normal mesothelial cells. The observed elevated expression of an oncogene that encodes a growth factor is suggestive for the concept of autocrine growth stimulation of tumor cells. A prerequisite for an autocrine function of the c-sis oncogene is the presence of receptors for this growth factor. Therefore we studied the presence of the PDGF B-type receptor mRNA in malignant and normal mesothelial cells. The malignant mescthelioma cell lines had a strongly elevated expression of the PDGF B-type receptor compared to normal mesothelial cells. In conclusion, human malignant mesothelioma cell lines express strongly the PDGF B (c-sis) oncogene and the PDGF B-type receptor. This study indicates that the c-sis oncogene can function as an autocrine growth factor in human malignant mesotheliomas. Supported by the Netherlands Cancer Foundation (Koningin Wilhelmina Fends).
Abstracts 132
M A L I G N A N T PLEURAL MESOTHELIOMA: C H R O M O S O M E A N D D N A ANALYSIS. M. TiainenL L. Tammilehto 2,K. Mattson 2,~.Kere I,and S. Knuutila~.IDepartment of Medical Genetics,University of Helsinki, and 2Department of Pulmonary Medicine, Helsinki University Central Hospital, Helsinki, Finland.
Successful cytogenetic studies were performed on tumor and/or pleural fluid samples from 34 out of 38 patients with malignant pleural mesothelioma. Clonal chromosome abnormalities were detected in 25 patients, 19 of them studied before treatment. Most of the karyotypic findings were complex including several structural and numerical aberrations, and no single abnormality common to all 25 patients was seen. Chromosomes most frequently involved in abnormalities were 1, 3, 7, 9,11,14 and 22. Partial or total polysomies of #7 (13 patients) and #11 (11 patients) and partial or total monosomies of @3 (12 patients), @9 (12 patients), #14 (11 patients) and #22 (14 patients) as well as translocations and deletions involving bands lp11-22 (11 patients) seem to be nonrandom abnormalities in mesothelioma. Based on the cytogenetic findings the study has been carried on to molecular level. Southern blot hybridization analyses have been performed on DNA samples from tumors of 26 patients. The following chromosome 7 genes have thus far been screened for rearrangements and amplifications: MET oncogene, multiple drug resistance gene, epidermal growth factor receptor gene (ERB-B oncogene), platelet derived growth factor gene, and plasminogen activator inhibitor gene. Instances of gene amplifications have been seen.
133
EXPRESSION OF THE PDGF B- (C-SIS} A N D PDGF A-CHAIN GENES A N D THE PDGF B-TYPE RECEPTOR IN H U M A N M A L I G N A N T M E S O T H E L I O M A CELL LINES. M. A. VersnelI,M. J.Bouts I, H. C. Hoogsteden 2,Th. H. van der Kwast 3,and A. Hagemeijer ~.~Department of Cell Biology, Immunology and Genetics, 2Department of Pulmonary Diseases, 3Department of Pathology, Erasmus University and Academic Hospital Dijkzigt,Rotterdam, The Netherlands.
Malignant mesotheliomas are mesodermally derived tumors. In a panel of malignant mesothelioma cell lines from patients with a confirmed malignant mesothelioma we studied the expression of the PDGF B-(c-sis) and PDGF A-chain genes. Cultured normal mesotheliai cells were used as a control. The malignant mesothelioma cell lines clearly expressed the 4.0 kb c-sis mRNA while the normal mesothelial cell lines did not express this messenger. The PDGF A-chain expression was only slightly elevated in the malignant mesothelioma cell lines compared to normal mesothelial cells. The observed elevated expression of an oncogene that encodes a growth factor is suggestive for the concept of autocrine growth stimulation of tumor cells. A prerequisite for an autocrine function of the c-sis oncogene is the presence of receptors for this growth factor. Therefore we studied the presence of the PDGF B-type receptor mRNA in malignant and normal mesothelial cells. The malignant mescthelioma cell lines had a strongly elevated expression of the PDGF B-type receptor compared to normal mesothelial cells. In conclusion, human malignant mesothelioma cell lines express strongly the PDGF B (c-sis) oncogene and the PDGF B-type receptor. This study indicates that the c-sis oncogene can function as an autocrine growth factor in human malignant mesotheliomas. Supported by the Netherlands Cancer Foundation (Koningin Wilhelmina Fends).