This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Negrini, M. Articles by Barbanti-Brodano, G. Search for Related Content PubMed PubMed Citation Articles by Negrini, M. Articles by Barbanti-Brodano, G.

Suppression of Tumorigenicity and Anchorage-independent Growth of BK Virus-transformed Mouse Cells by Human Chromosome 11¹

Institute of Microbiology [M. N., J. V. P., S. S., A. Co., F. G., P. R., G. B-B.], Interdepartment Center for Cancer Research [M. N., A. Ca.], and Institute of Medical Genetics [A. B., C. G., A. S.], School of Medicine, University of Ferrara, Via Luigi Borsari 46, I-44100 Ferrara, Italy; and Department of Microbiology and Molecular Genetics [D. A., E. J. S.], University of California at Irvine, Irvine, California 92717

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."

¹ This work was supported by grants to G.B-B. from Associazione Italiana per la Ricerca sul Cancro (AIRC), Special Project "Tumor Suppressor Genes," and from Consiglio Nazionale delle Ricerche, Progetto Finalizzato "Applicazioni Cliniche della Ricerca Oncologica" (ACRO), and by grant 19104 to E. J. S. from the National Cancer Institute.

² Supported by fellowships from the Consorzio Interuniversitario Nazionale per la Bio-Oncologia (CINBO).

³ Supported by a fellowship from the Ministero degli Esteri Italiano.

⁴ Supported by a fellowship from the Associazione Italiana per la Ricerca sul Cancro.

⁵ To whom requests for reprints should be addressed.

Received 8/28/91. Accepted 12/13/91.