SUPPRESSION OF TRANSFORMED PHENOTYPE AND TUMORIGENICITY AFTER TRANSFER OF CHROMOSOME-4 INTO U251 HUMAN GLIOMA-CELLS

Citation
Ma. Pershouse et al., SUPPRESSION OF TRANSFORMED PHENOTYPE AND TUMORIGENICITY AFTER TRANSFER OF CHROMOSOME-4 INTO U251 HUMAN GLIOMA-CELLS, Genes, chromosomes & cancer, 20(3), 1997, pp. 260-267
Citations number
43
Categorie Soggetti
Oncology,"Genetics & Heredity
Journal title
ISSN journal
10452257
Volume
20
Issue
3
Year of publication
1997
Pages
260 - 267
Database
ISI
SICI code
1045-2257(1997)20:3<260:SOTPAT>2.0.ZU;2-Y
Abstract
The development of primary human brain tumors, particularly glioblasto ma multiforme (GBM), has been associated with a number of molecular an d chromosomal abnormalities. In this study, a novel tumor suppressor l ocus was identified and localized after the transfer of a human chromo some 4 into U251 human GBM cells. Hybrid clones containing a transferr ed neomycin-resistance tagged chromosome 4 revealed an inability to fo rm tumors in nude mice and a greatly decreased efficiency of soft agar ose colony formation. As a control, clones containing a transferred ch romosome 2 were generated, and these retained the tumorigenic phenotyp e of the parental U251 cells. The presence of the transferred chromoso mes was demonstrated by gain of polymorphic loci and FISH analyses. Se veral suppressed hybrid clones were shown to contain spontaneously red uced versions of the transferred chromosome 4. A common region of the fragmented chromosome 4 was retained among these clones that included the epidermal growth factor locus at 4q24-26 and several adjacent mark ers. The identification of a common fragment in the suppressed clones suggests the presence of a tumor suppressor gene or genes in this regi on, involved in glioma oncogenesis. (C) 1997 Wiley-Liss, Inc.