Growth factor biomarkers associated with estrogen- and radiation-induced breast cancer progression

Breast cancer is the most common cancer in women worldwide. Transformation of a normal cell to a malignant one results from mutations in genes that encode key regulatory proteins. Growth factors are proteins secreted by a variety of transformed cells and tumors and function as autocrine regulators of growth. Biomarkers associated with cancer were examined in human breast epithelial cells transformed by high-LET radiation in the presence of 17beta-estradiol. An established cancer model was used in these studies. The MCF-10F cells that were irradiated with double doses of alpha-particles in the presence of estrogen (60 cGy + E/60 cGy + E, named Alpha 5) showed gradual phenotypic changes relative to control, including tumorigenicity in heterologous animals. Protein expression was determined by quantification of immunofluorescence staining coupled with confocal microscopy. The transforming growth factor alpha, epidermal growth factor, ERK1 and fibroblast growth factor-1 (Int2) protein expression was analyzed. Increased protein expression was observed in non-tumorigenic and tumorigenic alpha-irradiated and estrogen-treated cells. However, Stat-1alpha and pS2 protein expression was only increased in the tumorigenic Alpha 5 and Tumor 2 cell lines. It can be concluded that high-LET radiation in the presence of estrogen-induced changes in the proteins associated with growth factors and their overexpression may be a critical step in the cascade of events that characterize progression in breast cancer.