Artikel
Identification of genes, biological processes and pathways involved in the chromosome 6 mediated suppression of tumorigenicity in MDA-MB-231 breast cancer cells
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Veröffentlicht: | 20. März 2006 |
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Background: Several cytogenetic studies demonstrated frequent allelic losses at defined regions on chromosome 6 in breast tumors, suggesting the presence of tumor suppressor genes (TSGs) contributing to breast cancer tumorigenesis. Different techniques identified several candidate TSGs on chromosome 6 in breast cancer, but no functional evidence for a TSG function for these genes could be supplied so far.
Method: In order to identify key genes and elucidate the regulatory pathways that are involved in the development and progression of breast cancer, we combined array-based expression profiling with the microcell mediated transfer of chromosome 6 into MDA-MB-231 breast cancer cells.
Results: Microcell mediated transfer of chromosome 6 into MDA-MB-231 breast cancer cells resulted in hybrids characterised by reduced anchorage dependent growth and a strongly reduced tumorigenicity in nude mice. Comparing the expression profiles of tumorigenic parental cells and non-tumorigenic hybrids we identified a defined set of genes involved in chromosome 6 mediated breast cancer suppression. These genes could be integrated into biological processes and pathways known to be involved in breast cancer development. Overexpression and knock down of single genes of the identified gene set in breast and other cancer cell lines are used to further elucidate their role in cancer development and / or progression.
Conclusions: Our results provide functional evidence, that the suppression of the tumorigenic phenotype of the breast cancer cell line MDA-MB-231 is mediated by a set of genes / pathways regulated by one or more genes on chromosome 6.