Genetic background of different cancer cell lines influences the gene set involved in chromosome 8 mediated breast tumor suppression.
Several lines of evidence suggest that chromosome 8 is likely to harbor tumor-suppressor genes involved in breast cancer. We showed previously that microcell-mediated transfer of human chromosome 8 into breast cancer cell line MDA-MB-231 resulted in reversion of these cells to tumorigenicity and was accompanied by changes in the expression of a breast cancer-relevant gene set. In the present study, we demonstrated that transfer of human chromosome 8 into another breast cancer cell line, CAL51, strongly reduced the tumorigenic potential of these cells. Loss of the transferred chromosome 8 resulted in reappearance of the CAL51 phenotype. Microarray analysis identified 78 probe sets differentially expressed in the hybrids compared with in the CAL51 and the rerevertant cells. This signature was also reflected in a panel of breast tumors, lymph nodes, and distant metastases and was correlated with several prognostic markers including tumor size, grading, metastatic behavior, and estrogen receptor status. The expression patterns of seven genes highly expressed in the hybrids but down-regulated in the tumors and metastases (MYH11, CRYAB, C11ORF8, PDGFRL, PLAGL1, SH3BP5, and KIAA1026) were confirmed by RT-PCR and tissue microarray analyses. Unlike with the corresponding nontumorigenic phenotypes demonstrated for the MDA-MB-231- and CAL51-derived microcell hybrids, the respective differentially expressed genes strongly differed. However, the majority of genes in both gene sets could be integrated into a similar spectrum of biological processes and pathways, suggesting that alterations in gene expression are manifested at the level of functions and pathways rather than in individual genes.
Department of Tumor Genetics, Max Delbrueck Center for Molecular Medicine, Robert Roessle Str. 10, 13092 Berlin, Germany. sseitz@mdc-berlin.de
Susanne
S
Seitz
Eberhard
E
Korsching
Jörg
J
Weimer
Anja
A
Jacobsen
Norbert
N
Arnold
Alfons
A
Meindl
Wolfgang
W
Arnold
Dirk
D
Gustavus
Christiane
C
Klebig
Iver
I
Petersen
Siegfried
S
Scherneck
D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002898:Chromosomes, Human, Pair 8; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D018014:Gene Transfer Techniques; D016147:Genes, Tumor Suppressor; D006801:Humans; D006822:Hybrid Cells; D051379:Mice; D008819:Mice, Nude; D046228:Microarray Analysis; D018895:Microsatellite Repeats; D009362:Neoplasm Metastasis; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation