Abstract

Identification of markers with the potential to predict tumorigenic behavior is important in breast cancer, due to the variability in clinical disease progression. Genetic alterations during neoplastic progression may appear as changes in total DNA content, single genes, or gene expression. Oncogenic alterations are thought to be prognostic indices for patients with breast cancer. Breast cancer deregulation can occur in the normal cellular process and can be measured by microsatellite instability (MSI)/loss of heterozygosity (LOH). Chromosome 11 is unique in this respect, as three regions of MSI/LOH have been identified (11p15-p15.5, 11q13-q13.3 and 11q23-q24). There are many important families of genes, such as FGF, CCND1, FADD, BAD and GAD2, that are located on chromosome 11 and these play a crucial role in breast cancer progression. Among them, different members of the fibroblast growth factor (FGF) family of genes are clustered around human chromosome 11q13 amplicon, which are constantly altering during breast cancer progression. Therefore, in this study, locus 11q13 and FGF3 gene (11q13) function were investigated in a radiation and estrogen breast cancer model induced by high-LET (a-particle) radiation and estrogen exposure. To assess the effect of ionizing radiation and estrogen at chromosome 11q13 loci and the subsequent role of FGF3 gene expression, various microsatellite markers were chosen in this region, and allelic loses (similar to 20-45%) were identified by PCR-SSCP analysis. Results showed an increase in FGF3 protein expression and a 6- to 8-fold change in gene expression of FGF3 and associated genes. These deregulations could be utilized as an appropriate target for therapeutic intervention in breast cancer.