Skip to main content
The EMBO Journal logoLink to The EMBO Journal
. 1986 Dec 20;5(13):3461–3466. doi: 10.1002/j.1460-2075.1986.tb04670.x

Introduction of human chromosome 11 via microcell transfer controls tumorigenic expression of HeLa cells.

P J Saxon, E S Srivatsan, E J Stanbridge
PMCID: PMC1167381  PMID: 2881780

Abstract

Both tumorigenic segregant HeLa X human fibroblast hybrids and tumorigenic HeLa (D98/AH-2) cells can be converted to a non-tumorigenic state following introduction of a single copy of a fibroblast t(X;11) chromosome. The translocated chromosome contains approximately 95% of the 11 chromosome and the q26-qter portion of the X chromosome which contains the hypoxanthine guanine phosphoribosyl transferase (HPRT) gene. Introduction of a human X chromosome has no effect on tumorigenic expression. Suppression of tumorigenicity is relieved by selecting cells which have lost the t(X;11) chromosome by growth in medium containing 6-thioguanine (6-TG). Further, reintroduction of the t(X;11) chromosome into tumorigenic 6TGR cells again suppresses tumorigenicity. Thus, the introduction of a single copy of a human chromosome 11 is sufficient to completely suppress the tumorigenic phenotype of HeLa cells and is suggestive of the presence of tumor-suppressor gene(s) on this chromosome.

Full text

PDF

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BARSKI G., SORIEUL S., CORNEFERT F. "Hybrid" type cells in combined cultures of two different mammalian cell strains. J Natl Cancer Inst. 1961 May;26:1269–1291. [PubMed] [Google Scholar]
  2. Evans E. P., Burtenshaw M. D., Brown B. B., Hennion R., Harris H. The analysis of malignancy by cell fusion. IX. Re-examination and clarification of the cytogenetic problem. J Cell Sci. 1982 Aug;56:113–130. doi: 10.1242/jcs.56.1.113. [DOI] [PubMed] [Google Scholar]
  3. Harris H., Miller O. J., Klein G., Worst P., Tachibana T. Suppression of malignancy by cell fusion. Nature. 1969 Jul 26;223(5204):363–368. doi: 10.1038/223363a0. [DOI] [PubMed] [Google Scholar]
  4. Harris H., Wiener F., Klein G. The analysis of malignancy by cell fusion. 3. Hybrids between diploid fibroblasts and other tumour cells. J Cell Sci. 1971 May;8(3):681–692. doi: 10.1242/jcs.8.3.681. [DOI] [PubMed] [Google Scholar]
  5. Harris H., Zalik S. E. Studies on the endogenous galactose-binding lectin during early development of the embryo of Xenopus laevis. J Cell Sci. 1985 Nov;79:105–117. doi: 10.1242/jcs.79.1.105. [DOI] [PubMed] [Google Scholar]
  6. Kaelbling M., Klinger H. P. Suppression of tumorigenicity in somatic cell hybrids. III. Cosegregation of human chromosome 11 of a normal cell and suppression of tumorigenicity in intraspecies hybrids of normal diploid x malignant cells. Cytogenet Cell Genet. 1986;41(2):65–70. doi: 10.1159/000132206. [DOI] [PubMed] [Google Scholar]
  7. Kaelbling M., Roginski R. S., Klinger H. P. DNA polymorphisms indicate loss of heterozygosity for chromosome 11 of D98AH2 cells. Cytogenet Cell Genet. 1986;41(4):240–244. doi: 10.1159/000132236. [DOI] [PubMed] [Google Scholar]
  8. Klinger H. P. Suppression of tumorigenicity. Cytogenet Cell Genet. 1982;32(1-4):68–84. doi: 10.1159/000131688. [DOI] [PubMed] [Google Scholar]
  9. Knudson A. G., Jr Hereditary cancer, oncogenes, and antioncogenes. Cancer Res. 1985 Apr;45(4):1437–1443. [PubMed] [Google Scholar]
  10. Koufos A., Hansen M. F., Lampkin B. C., Workman M. L., Copeland N. G., Jenkins N. A., Cavenee W. K. Loss of alleles at loci on human chromosome 11 during genesis of Wilms' tumour. Nature. 1984 May 10;309(5964):170–172. doi: 10.1038/309170a0. [DOI] [PubMed] [Google Scholar]
  11. McNeill C. A., Brown R. L. Genetic manipulation by means of microcell-mediated transfer of normal human chromosomes into recipient mouse cells. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5394–5398. doi: 10.1073/pnas.77.9.5394. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Murphree A. L., Benedict W. F. Retinoblastoma: clues to human oncogenesis. Science. 1984 Mar 9;223(4640):1028–1033. doi: 10.1126/science.6320372. [DOI] [PubMed] [Google Scholar]
  13. Scott A. F., Phillips J. A., 3rd, Migeon B. R. DNA restriction endonuclease analysis for localization of human beta- and delta-globin genes on chromosome 11. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4563–4565. doi: 10.1073/pnas.76.9.4563. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Shih C., Weinberg R. A. Isolation of a transforming sequence from a human bladder carcinoma cell line. Cell. 1982 May;29(1):161–169. doi: 10.1016/0092-8674(82)90100-3. [DOI] [PubMed] [Google Scholar]
  15. Stanbridge E. J. A case for human tumor-suppressor genes. Bioessays. 1985 Dec;3(6):252–255. doi: 10.1002/bies.950030605. [DOI] [PubMed] [Google Scholar]
  16. Stanbridge E. J., Flandermeyer R. R., Daniels D. W., Nelson-Rees W. A. Specific chromosome loss associated with the expression of tumorigenicity in human cell hybrids. Somatic Cell Genet. 1981 Nov;7(6):699–712. doi: 10.1007/BF01538758. [DOI] [PubMed] [Google Scholar]
  17. Stanbridge E. J. Mycoplasma detection-an obligation to scientific accuracy. Isr J Med Sci. 1981 Jul;17(7):563–568. [PubMed] [Google Scholar]
  18. Stanbridge E. J. Suppression of malignancy in human cells. Nature. 1976 Mar 4;260(5546):17–20. doi: 10.1038/260017a0. [DOI] [PubMed] [Google Scholar]
  19. Weissman B., Stanbridge E. J. Characterization of ouabain resistant, hypoxanthine phosphoribosyl transferase deficient human cells and their usefulness as a general method for the production of human cell hybrids. Cytogenet Cell Genet. 1980;28(4):227–239. doi: 10.1159/000131536. [DOI] [PubMed] [Google Scholar]

Articles from The EMBO Journal are provided here courtesy of Nature Publishing Group

RESOURCES