PMID: 7520270Jun 1, 1994Paper

Induction of senescence and control of tumorigenicity in BK virus transformed mouse cells by human chromosome 6

Genes, Chromosomes & Cancer
F GualandiG Barbanti-Brodano

Abstract

Viral transformation models may be useful to detect and map human tumor suppressor genes. BK virus (BKV), a human papovavirus, readily transforms rodent cells but is unable to transform human cells, suggesting that oncosuppressive functions expressed in human cells control BKV oncogenic activity. We have transferred human chromosome 6 to BKV-transformed mouse pRPcT1ss1 cells. The great majority of the colonies growing in selective medium degenerated by senescence. Only five hybrid pRPcT1ss1/H6 clones maintained the immortalized phenotype of the recipient cell line. All the immortalized clones had two common regions of deletion involving bands 6q21-22 and the SOD2 gene in 6q25. Senescent colonies carried an intact chromosome 6. A specific human sequence in 6q21-22 was amplified by PCR in senescent cells, suggesting that this region harbors a gene inducing senescence. The SOD2 deletion confirms recent data on the role of the Mn-dependent superoxide dismutase in inhibition of proliferation. The monochromosomic hybrids bearing a deleted chromosome 6 showed a reverted phenotype in vitro and a significantly longer latency period before they were tumorigenic in nude mice, indicating the presence of a tumor suppressor gene in the resid...Continue Reading

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