Genomic and expression analysis of the 8p11-12 amplicon in human breast cancer cell lines.
Gene amplification is an important mechanism of oncogene activation in breast and other cancers. Characterization of amplified regions of the genome in breast cancer has led to the identification of important oncogenes including erbB-2/HER-2, C-MYC, and fibroblast growth factor receptor (FGFR) 2. Chromosome 8p11-p12 is amplified in 10-15% of human breast cancers. The putative oncogene FGFR1 localizes to this region; however, we show evidence that FGFR inhibition fails to slow growth of three breast cancer cell lines with 8p11-p12 amplification. We present a detailed analysis of this amplicon in three human breast cancer cell lines using comparative genomic hybridization, traditional Southern and Northern analysis, and chromosome 8 cDNA microarray expression profiling. This study has identified new candidate oncogenes within the 8p11-p12 region, supporting the hypothesis that genes other than FGFR1 may contribute to oncogenesis in breast cancers with proximal 8p amplification.
Ray
Michael E
ME
Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, Michigan 48109-0948, USA.
Yang
Zeng Quan
ZQ
Albertson
Donna
D
Kleer
Celina G
CG
Washburn
Joseph G
JG
Macoska
Jill A
JA
Ethier
Stephen P
SP
D015139:Blotting, Southern; D001943:Breast Neoplasms / Q000235:genetics*; D002874:Chromosome Mapping; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D005819:Genetic Markers; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D009857:Oncogenes; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics; D014407:Tumor Cells, Cultured
D018076:DNA, Complementary; D005819:Genetic Markers; D017468:Receptors, Fibroblast Growth Factor; C496348:FGFR1 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1