Transfection with Plasmid PSV2gptEJ Induces Chromosome Rearrangements in CHEF Cells

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1987 Jan 1

PMID 3540955

Citations 12

Authors

G Stenman

E O Delorme

C C Lau

R Sager

Affiliations

Soon will be listed here.

Abstract

In previous cytogenetic studies, trisomy for 3q was found to be the most frequent chromosome change associated with induced tumorigenicity by a variety of agents in Chinese hamster cells. Here we describe similar chromosome changes in 11 lines of CHEF/18 cells transfected with the mutant c-Ha-ras containing plasmid pSV2gptEJ. All 11 lines contained the transfected EJ gene and expressed increased levels of p21, the EJ gene product. Ten of the 11 lines were tumorigenic and all but 2 of these were trisomic for all or part of 3q. One line remained diploid and was nontumorigenic despite expressing elevated p21. Two tumorigenic lines from "hit-and-run" transfection with pSV2gpt were shown to express only control levels of p21, but they were trisomic for 3q. These results show that increased p21 expression is neither necessary nor sufficient for inducing tumorigenicity of CHEF cells. We propose that tumorigenicity in the transfected CHEF/18 cells of this study was induced by chromosome rearrangements, especially trisomy for 3q, that occurred at increased frequencies following transfection with pSV2gptEJ.

Citing Articles

New tricks from an old oncogene: gene fusion and copy number alterations of MYB in human cancer.

Stenman G, Andersson M, Andren Y Cell Cycle. 2010; 9(15):2986-95.

PMID: 20647765 PMC: 3040924. DOI: 10.4161/cc.9.15.12515.

Nf1-deficient mouse Schwann cells are angiogenic and invasive and can be induced to hyperproliferate: reversion of some phenotypes by an inhibitor of farnesyl protein transferase.

Kim H, Ling B, Ratner N Mol Cell Biol. 1997; 17(2):862-72.

PMID: 9001241 PMC: 231813. DOI: 10.1128/MCB.17.2.862.

The human Ha-ras oncogene induces genomic instability in murine fibroblasts within one cell cycle.

Denko N, Giaccia A, Stringer J, Stambrook P Proc Natl Acad Sci U S A. 1994; 91(11):5124-8.

PMID: 8197195 PMC: 43944. DOI: 10.1073/pnas.91.11.5124.

Cancer genes: rare recombinants instead of activated oncogenes (a review).

Duesberg P Proc Natl Acad Sci U S A. 1987; 84(8):2117-24.

PMID: 3550807 PMC: 304600. DOI: 10.1073/pnas.84.8.2117.

Analysis of metastatic competence of mouse bladder carcinoma cells after transfection with activated Ha-ras or N-ras oncogenes.

Pohl J, FRANKS L, Schirrmacher V J Cancer Res Clin Oncol. 1988; 114(4):373-9.

PMID: 3410877 DOI: 10.1007/BF02128181.

References

Harrison J, Anisowicz A, Gadi I, Raffeld M, Sager R . Azacytidine-induced tumorigenesis of CHEF/18 cells: correlated DNA methylation and chromosome changes. Proc Natl Acad Sci U S A. 1983; 80(21):6606-10. PMC: 391218. DOI: 10.1073/pnas.80.21.6606. View

Ray F, Bartholdi M, Kraemer P, Cram L . Spontaneous in vitro neoplastic evolution: recurrent chromosome changes of newly immortalized Chinese hamster cells. Cancer Genet Cytogenet. 1986; 21(1):35-51. DOI: 10.1016/0165-4608(86)90199-8. View

Sager R, Tanaka K, Lau C, Ebina Y, Anisowicz A . Resistance of human cells to tumorigenesis induced by cloned transforming genes. Proc Natl Acad Sci U S A. 1983; 80(24):7601-5. PMC: 534388. DOI: 10.1073/pnas.80.24.7601. View

Kakati S, Sinha A . Banding patterns of Chinese hamster chromosomes. Genetics. 1972; 72(2):357-62. PMC: 1212832. DOI: 10.1093/genetics/72.2.357. View

Gadi I, Harrison J, Sager R . Genetic analysis of tumorigenesis: XVI. Chromosome changes in azacytidine- and insulin-induced tumorigenesis. Somat Cell Mol Genet. 1984; 10(5):521-9. DOI: 10.1007/BF01534856. View

Varmus H . The molecular genetics of cellular oncogenes. Annu Rev Genet. 1984; 18:553-612. DOI: 10.1146/annurev.ge.18.120184.003005. View

Lau C, Gadi I, Kalvonjian S, Anisowicz A, Sager R . Plasmid-induced "hit-and-run" tumorigenesis in Chinese hamster embryo fibroblast (CHEF) cells. Proc Natl Acad Sci U S A. 1985; 82(9):2839-43. PMC: 397661. DOI: 10.1073/pnas.82.9.2839. View

Oshimura M, Gilmer T, Barrett J . Nonrandom loss of chromosome 15 in Syrian hamster tumours induced by v-Ha-ras plus v-myc oncogenes. Nature. 1985; 316(6029):636-9. DOI: 10.1038/316636a0. View

Sager R, Kovac P . Genetic analysis of tumorigenesis: I. Expression of tumor-forming ability in hamster hybrid cell lines. Somatic Cell Genet. 1978; 4(3):375-92. DOI: 10.1007/BF01542849. View

10.

Kitchin R, Sager R . Genetic analysis of tumorigenesis: VI. Chromosome rearrangements in tumors derived from diploid premalignant Chinese hamster cells in nude mice. Somatic Cell Genet. 1980; 6(5):615-30. DOI: 10.1007/BF01538641. View

11.

Stanbridge E, Flandermeyer R, Daniels D, Nelson-Rees W . Specific chromosome loss associated with the expression of tumorigenicity in human cell hybrids. Somatic Cell Genet. 1981; 7(6):699-712. DOI: 10.1007/BF01538758. View

12.

Shih C, Weinberg R . Isolation of a transforming sequence from a human bladder carcinoma cell line. Cell. 1982; 29(1):161-9. DOI: 10.1016/0092-8674(82)90100-3. View

13.

Furth M, Davis L, Fleurdelys B, Scolnick E . Monoclonal antibodies to the p21 products of the transforming gene of Harvey murine sarcoma virus and of the cellular ras gene family. J Virol. 1982; 43(1):294-304. PMC: 256120. DOI: 10.1128/JVI.43.1.294-304.1982. View

14.

Kitchin R, Gadi I, Smith B, Sager R . Genetic analysis of tumorigenesis: X. Chromosome studies of transformed mutants and tumor-derived CHEF/18 cells. Somatic Cell Genet. 1982; 8(5):677-89. DOI: 10.1007/BF01542860. View

15.

Marshall C, Kitchin R, Sager R . Genetic analysis of tumorigenesis: XII. Genetic control of the anchorage requirement in CHEF cells. Somatic Cell Genet. 1982; 8(6):709-21. DOI: 10.1007/BF01543013. View

16.

Klinger H, Shows T . Suppression of tumorigenicity in somatic cell hybrids. II. Human chromosomes implicated as suppressors of tumorigenicity in hybrids with Chinese hamster ovary cells. J Natl Cancer Inst. 1983; 71(3):559-69. View

17.

Bishop J . Cellular oncogenes and retroviruses. Annu Rev Biochem. 1983; 52:301-54. DOI: 10.1146/annurev.bi.52.070183.001505. View

18.

Stenman G, Mark J . Loss of the Y chromosome in a cultured human salivary-gland adenocarcinoma. J Oral Pathol. 1983; 12(6):458-64. DOI: 10.1111/j.1600-0714.1983.tb00357.x. View