Suppression of transformation and tumorigenicity after transfer of chromosome 4 into glioblastoma multiforme cell line
- Univ. of Texas M.D. Anderson Cancer Center, Houston, TX (United States)
Locations of tumor suppressor genes have primarily been found based upon chromosomal alterations or deletions and allelic deletions. Evidence for tumor suppressor genes has also been provided by mono-chromosomal transfer of implicated chromosomes into tumor cells and demonstrated a suppression of their malignant phenotype. We have demonstrated that the transfer of chromosome 10 into the human glioblastoma cell line, U251, suppressed its tumorigenic phenotype. As part of this study, chromosomes 2 and 4 were introduced into U251 cells by microcell-mediated chromosomal transfer. Cells containing a transferred chromosome 2 failed to alter their tumorigenic phenotype. The hybrid clones containing a transferred chromosome 4 exhibited an unexpected suppression of their transformed and tumorigenic phenotype in vivo and in vitro (previous molecular and cytogenetic analyses have shown only a 20 to 30% frequency of alterations to chromosome 4 (considered random) in human gliomas). The presence of novel chromosomes was confirmed by molecular and karyotypic analyses. The hybrid cells containing a transferred chromosome 4 displayed a significant decrease in their saturation density, a decrease in their exponential growth rate, and an altered cellular morphology. The hybrid cells failed to proliferate in soft agarose. The introduction of chromosome 4 completely suppressed tumor formation when the hybrid cells were injected into nude mice. These findings indicate that chromosome 4 is the possible site of a tumor suppressor gene that is directly involved in glioma oncogenesis.
- OSTI ID:
- 133557
- Report Number(s):
- CONF-941009-; ISSN 0002-9297; TRN: 95:005313-0285
- Journal Information:
- American Journal of Human Genetics, Vol. 55, Issue Suppl.3; Conference: 44. annual meeting of the American Society of Human Genetics, Montreal (Canada), 18-22 Oct 1994; Other Information: PBD: Sep 1994
- Country of Publication:
- United States
- Language:
- English
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