| Abstract: |
We used standard karyotypic analyses of first‐division cells to identify a subpopulation of cells in primary malignant gliomas with over‐representation of chromosomes 7 and 22. These cells are a minor subpopulation in the primary tumor but become the dominant population after treatment in vitro of the cells with the chemotherapeutic agent 1,3‐bis(2‐chloroethyl)‐1‐nitrosourea (BCNU). The selection for a cell with this specific karyotypic abnormality suggests that these chromosomes contain genes important to the growth of BCNU‐resistant cells. Southern blot hybridization analyses demonstrate an increased copy number of the genes encoding platelet‐derived growth factor (PDGF) A‐chain and B‐chain, which have been mapped to chromosomes 7 and 22, respectively. Reverse transcription followed by polymerase chain reaction (RT‐PCR) analysis demonstrates increased expression of these genes. In addition, these cells secrete a mitogenic factor that stimulates 3H‐thymidine uptake in NIH 3T3 cells. This factor is sensitive to anti‐PDGF antibodies and β‐mercaptoethanol, but not to anti‐EGF antibodies. These data suggest that autocrine and/or paracrine mechanisms occur in human malignant gliomas, and that over‐expression of PDGF may play a role in the growth of BCNU‐resistant cells in these tumors. © 1993 Wiley‐Liss, Inc. Copyright © 1993 Wiley‐Liss, Inc., A Wiley Company |
| Keywords: |
platelet derived growth factor; human cell; nonhuman; glioma; polymerase chain reaction; animal cell; mouse; gene expression; tumor markers, biological; mitogenesis; cytogenetics; drug resistance; tumor cells, cultured; carmustine; animalia; cancer resistance; gene mapping; gene expression regulation, neoplastic; molecular sequence data; glioblastoma; cell subpopulation; platelet-derived growth factor; dna, neoplasm; base sequence; chromosome aberrations; karyotype; karyotyping; rna, neoplasm; receptors, platelet-derived growth factor; chromosome 7; chromosome 22; chromosomes, human, pair 22; growth substances; chromosomes, human, pair 7; ploidies; blotting, southern; human; article; support, u.s. gov't, p.h.s.
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