Journal Article

Recurrent alterations of the short arm of chromosome 3 define a tumor suppressor region in rat mammary tumor cells

Nicholas C. Popescu and John W. Greiner

in Carcinogenesis

Volume 20, issue 10, pages 2033-2036
Published in print October 1999 | ISSN: 0143-3334
Published online October 1999 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/20.10.2033
Recurrent alterations of the short arm of chromosome 3 define a tumor suppressor region in rat mammary tumor cells

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  • Clinical Cytogenetics and Molecular Genetics

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Cytogenetic alterations associated with different stages in carcinogenesis can be distinguished in cultured human or rodent cells transformed by carcinogenic agents. Three tumorigenic rat mammary epithelial cell lines transformed in vitro with 7,12,-dimethylbenz[a]anthracene alone or in combination with 12-O-tetradecanoylphorbol-13-acetate were examined cytogenetically. Non-random alterations consisting of translocations involving the short arm of chromosome 3 and trisomy of chromosomes 14 and X were identified in all three lines. Deletion and inversion of chromosome 1 with the breakpoint at band 1q22 and a duplication 1q 32–43 and trisomy of chromosome 2 were observed in two cell lines. The accumulation of structural alterations and chromosome imbalances during the process of cell immortalization and acquisition of tumorigenicity are required for normal rat mammary cells to become malignant. Unbalanced translocations of chromosome 3 resulting in loss of the short arm had the breakpoint at 3p11. This site is a hotspot of breakage and recombination in various rat tumors and may represent a region of tumor suppressor gene critical to the development of rat mammary tumors, as well as other types of tumors.

Keywords: DMBA, 7,12-dimethylbenz[a]anthracene; FBS, fetal bovine serum; LOH, loss of heterozygosity; NMU, N-nitroso-N-methylurea; NOR, nucleolar organizer regions; TPA, 12-O-tetradecanoylphorbol-13-acetate.

Journal Article.  3197 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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