Microcell-mediated transfer of chromosome 6 into the breast cancer cell line MDA-MB-231: a specific set of genes is involved in the reversion of the tumorigenic phenotype

Background

Several cytogenetic studies demonstrated frequent allelic losses at defined regions on chromosome 6 in breast tumors, suggesting the presence of tumor suppressor gene(s) (TSG) contributing to breast cancer (BC) tumorigenesis. Different techniques identified several candidate TSGs on chromosome 6 in BC, but no functional evidence for a TSG function for these genes could so far be supplied. In order to identify key genes and elucidate the regulatory pathways that are involved in the development and progression of BC, we combined array-based expression profiling with a powerful functional approach, the microcell-mediated chromosome transfer.

Methods and results

An intact copy of chromosome 6 was transferred into the 6q deleted and highly invasive BC cell line MDA-MB-231 using the microcell-mediated chromosome transfer. It was demonstrated by microsatellite allelotyping, CGH and FISH that the hybrid clones contain two fragments of chromosome 6, spanning 6p22-q14 and 6q15-6q27. The transfer of parts of chromosome 6 into the MDA-MB-231 cells resulted in reduced anchorage-dependent growth, reduced in vitro invasion and a strongly reduced tumorigenic potential.

In order to identify genes responsible for the observed reversion of the tumorigenic phenotype in MDA-MB-231 cells, differential gene expression between the parental cell line and the hybrid clones was analysed using oligonucleotide micro-arrays (HG-U133; Affymetrix, Santa Clara, CA, USA). The identified set of differentially expressed genes will be presented.

Conclusions

Our results provide functional evidence that the suppression of the tumorigenic phenotype of the BC cell line MDA-MB-231 is mediated by a specific set of genes regulated by one or more genes on chromosome 6.