BCNU-resistant human glioma cells with over-representation of chromosomes 7 and 22 demonstrate increased copy number and expression of platelet-derived growth factor genes
✍ Scribed by Dr. Adrienne C. Scheck; Bipin M. Mehta; Melanie K. Beikman; Joan Rankin Shapiro
- Publisher
- John Wiley and Sons
- Year
- 1993
- Tongue
- English
- Weight
- 946 KB
- Volume
- 8
- Category
- Article
- ISSN
- 1045-2257
No coin nor oath required. For personal study only.
✦ Synopsis
We used standard karyotypic analyses of first-division cells t o 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 I ,3-bis(2-chloroethyl)-I -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 t o 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 t o anti-PDGF antibodies and P-mercaptoethanol. but not t o 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.