Suppression of tumorigenicity and anchorage-independent growth of BK virus-transformed mouse cells by human chromosome 11.
Viral transformation models may be useful for detecting and mapping 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 11 to BKV-transformed mouse cells. All of the cell clones were suppressed in the tumorigenic phenotype and anchorage-independent growth, except one clone which was nontumorigenic but maintained the ability to grow in soft agar. Cytogenetic analysis and DNA hybridization with chromosome 11-specific probes showed that all the reverted hybrids had an intact human chromosome 11, except the clone growing in semisolid medium which had lost the short arm. The results suggest that a gene located on 11p controls anchorage independence, whereas a gene on 11q controls the tumorigenicity of BKV-transformed cells. BKV T-antigen was expressed in all the hybrid clones at the same level as in the parental cell line, indicating that the putative human tumor suppressor gene(s) do not inhibit expression of the viral oncogene and must operate by another mechanism in inducing reversion of the oncogenic phenotype. Since BKV-transformed mouse cells are highly susceptible to retrovirus infection, this model can be used for searching and cloning tumor suppressor gene(s) by retrovirus-mediated "insertional mutagenesis".
Negrini
M
M
Institute of Microbiology, School of Medicine, University of Ferrara, Italy.
Castagnoli
A
A
Pavan
J V
JV
Sabbioni
S
S
Araujo
D
D
Corallini
A
A
Gualandi
F
F
Rimessi
P
P
Bonfatti
A
A
Giunta
C
C
D000818:Animals; D001739:BK Virus; D002448:Cell Adhesion / Q000235:genetics; D002472:Cell Transformation, Viral / Q000235:genetics*; D002880:Chromosomes, Human, Pair 11; D004279:DNA, Viral; D016153:Genes, Suppressor / Q000502:physiology*; D006801:Humans; D051379:Mice; D009693:Nucleic Acid Hybridization; D013489:Suppression, Genetic / Q000235:genetics*
D004279:DNA, Viral