A network of clinically and functionally relevant genes is involved in the reversion of the tumorigenic phenotype of MDA-MB-231 breast cancer cells after transfer of human chromosome 8.
Several investigations have supposed that tumor suppressor genes might be located on human chromosome 8. We used microcell-mediated transfer of chromosome 8 into MDA-MB-231 breast cancer cells and generated independent hybrids with strongly reduced tumorigenic potential. Loss of the transferred chromosome results in reappearance of the malignant phenotype. Expression analysis identified a set of 109 genes (CT8-ps) differentially expressed in microcell hybrids as compared to the tumorigenic MDA-MB-231 and rerevertant cells. Of these, 44.9% are differentially expressed in human breast tumors. The expression pattern of CT8-ps was associated with prognostic factors such as tumor size and grading as well as loss of heterozygosity at the short arm of chromosome 8. We identified CT8-ps networks suggesting that these genes act cooperatively to cause reversion of tumorigenicity in MDA-MB-231 cells. Our findings provide a conceptual basis and experimental system to identify and evaluate genes and gene networks involved in the development and/or progression of breast cancer.
Seitz
Susanne
S
Department of Tumor Genetics, Max Delbrueck Center for Molecular Medicine, Robert Roessle Str. 10, 13125 Berlin, Germany. sseitz@mdc-berlin.de
Frege
Renate
R
Jacobsen
Anja
A
Weimer
Jörg
J
Arnold
Wolfgang
W
von Haefen
Clarissa
C
Niederacher
Dieter
D
Schmutzler
Rita
R
Arnold
Norbert
N
Scherneck
Siegfried
S
D001943:Breast Neoplasms / Q000235:genetics*; D045744:Cell Line, Tumor; D002874:Chromosome Mapping; D002898:Chromosomes, Human, Pair 8; D005260:Female; D018014:Gene Transfer Techniques; D005819:Genetic Markers; D006801:Humans; D019656:Loss of Heterozygosity; D008957:Models, Genetic; D010641:Phenotype
D005819:Genetic Markers