Selection of cells with different chromosomal localizations of the amplified c-myc gene during in vivo and in vitro growth of the breast carcinoma cell line SW 613-S.
The c-myc gene is amplified in the human breast carcinoma cell line SW 613-S. At early in vitro passages, the extra copies of the gene were mainly localized in double minute chromosomes (DMs), as shown by in situ hybridization with a biotinylated c-myc probe. However, cells without DMs were also present in which the c-myc genes were found integrated into any of several distinct chromosomes (mainly 7q+, 4 and 4q+, and 1). When this cell line was propagated in vitro, the level of c-myc amplification decreased because cells with DMs and a high amplification level were lost and replaced by cells without DMs and having a low amplification level. On the contrary, when early passage SW 613-S cells were grown in vivo, as subcutaneous tumours in nude mice, cells with numerous DMs and a high level of c-myc amplification were selected for. In one cell line (SW 613-Tu1) established from such a tumour, the DM-containing cells were substituted at late passages for cells with a high number of c-myc copies integrated within an abnormally banded region, at band 17q24 of a 17q+ chromosome. When only cells with integrated genes were present, this cell line was still highly tumorigenic indicating that the localization of the c-myc genes in DMs was not required for these cells to be tumorigenic in nude mice. Furthermore, cells of the secondary tumours induced by SW 613-Tu1 did not contain any DMs showing that in vivo growth did not promote the release of integrated c-myc copies into DMs.
Cherif
D
D
Laboratoire de Cytogénétique, U301 INSERM and UM7 CNRS, Centre Hayem, Hôpital Saint-Louis, Paris, France.
Lavialle
C
C
Modjtahedi
N
N
Le Coniat
M
M
Berger
R
R
Brison
O
O
D015139:Blotting, Southern; D001943:Breast Neoplasms / Q000235:genetics*; D015197:Carcinogenicity Tests; D002871:Chromosome Banding; D002874:Chromosome Mapping; D005260:Female; D005784:Gene Amplification; D006801:Humans; D015151:Immunoblotting; D009693:Nucleic Acid Hybridization; D011519:Proto-Oncogenes; D014407:Tumor Cells, Cultured