Loss of a Putative Tumor Suppressor Locus after Gamma-Ray-Induced Neoplastic Transformation of HeLa × Skin Fibroblast Human Cell Hybrids

作者: Marc S. Mendonca , Clare L. Fasching , Eri S. Srivatsan , Eric J. Stanbridge , J. Leslie Redpath

DOI: 10.2307/3578923

关键词: ChromosomeNeoplastic transformationChromosome 13Locus (genetics)HeLaTumor suppressor geneMolecular biologyFibroblastGeneticsBiologyCarcinogenesis

摘要: The nontumorigenic HeLa x skin fibroblast hybrid cell line, CGL1, can be induced to re-express tumor-associated surface antigen, p75-IAP (intestinal alkaline phosphatase), with resulting neoplastic transformation, by exposure gamma radiation. This has allowed the human system developed into a quantitative in vitro model for radiation-induced transformation of cells. Recently, several gamma-ray-induced IAP-expressing mutants (GIMs) CGL1 were isolated and all tumorigenic when injected subcutaneously nude mice (Mendonca et al., Cancer Res. 51, 4455-4462, 1991). Control lines which negative (CONs) also from irradiated populations, none found tumorigenic. We have now begun investigate molecular basis this studying potential genetic linkage between p75/IAP expression, tumorigenicity damage putative tumor suppressor locus on chromosome 11. Previous analysis rare spontaneous segregants indicated that is involved regulation expression marker intestinal phosphatase (p75-IAP) system. Therefore, restriction fragment length polymorphism painting been performed 11, 13 as control, p75/IAP-positive GIM p75/IAP-negative CON lines. report five eight GIMs large-scale 11's evident (four lost one complete copy 11 both copies heavily damaged). None CONs, however (0/5), either No control 13's was detected or CONs. data further suggest contain an active loss will result conclude it responsible at least part these

参考文章(47)
B C Misra, E S Srivatsan, Localization of HeLa cell tumor-suppressor gene to the long arm of chromosome II. American Journal of Human Genetics. ,vol. 45, pp. 565- 577 ,(1989)
B S Emanuel, M Raducha, P S Henthorn, C A Griffin, H Harris, M J Weiss, M Smith, Human placental and intestinal alkaline phosphatase genes map to 2q34-q37. American Journal of Human Genetics. ,vol. 41, pp. 1025- 1034 ,(1987)
P.J. Saxon, E.S. Srivatsan, E.J. Stanbridge, Introduction of human chromosome 11 via microcell transfer controls tumorigenic expression of HeLa cells. The EMBO Journal. ,vol. 5, pp. 3461- 3466 ,(1986) , 10.1002/J.1460-2075.1986.TB04670.X
S. P. Wilczynski, B. C. Misra, E. S. Srivatsan, Murali Venugopalan, Loss of heterozygosity for alleles on chromosome II in cervical carcinoma. American Journal of Human Genetics. ,vol. 49, pp. 868- 877 ,(1991)
J Downward, M F Greaves, P Parker, M A Baker, D R Sutherland, E J Stanbridge, D C Bicknell, M D Waterfield, Structural and functional features of a cell surface phosphoglycoprotein associated with tumorigenic phenotype in human fibroblast x HeLa cell hybrids. Journal of Biological Chemistry. ,vol. 261, pp. 2418- 2424 ,(1986) , 10.1016/S0021-9258(17)35952-5
Sattera Chandrashekharappa, E. S. Srivatsan, R. A. Jesudasan, R. A. Rahman, G. A. Evans, Deletion and translocation of chromosome 11q13 sequences in cervical carcinoma cell lines. American Journal of Human Genetics. ,vol. 56, pp. 705- 715 ,(1995)
Eric J. Stanbridge, J. Leslie Redpath, Kathryn M. Latham, Ronald J. Antoniono, Marc. S. Mendonca, Characterization of Intestinal Alkaline Phosphatase Expression and the Tumorigenic Potential of γ-irradiated HeLa × Fibroblast Cell Hybrids Cancer Research. ,vol. 51, pp. 4455- 4462 ,(1991)
Eldad Zacksenhaus, Rod Bremner, Zhe Jiang, R. Montgomery Gill, Michelle Muncaster, Mary Sopta, Robert A. Phillips, Brenda L. Gallle, Unraveling the Function of the Retinoblastoma Gene Advances in Cancer Research. ,vol. 61, pp. 115- 141 ,(1993) , 10.1016/S0065-230X(08)60957-4