Breast cancer is the most common
malignancy diagnosed among women and represents a heterogeneous group of subtypes.
Radiation therapy is a critical component of treatment for
breast cancer patients. However, little is known about radiation response among these intrinsic subtypes. In previous studies, we identified a significant induction of FAS after irradiation in biologically favorable
breast cancer patients and
breast cancer cell lines. Here, we expanded our study and investigated radiation response in a mouse model of
breast cancer. MCF7 (
luminal), HCC1954 (HER2+) or SUM159 (basal) cells were implanted orthotopically into the dorsal mammary fat pad of nude mice. These mice were then treated with different doses of radiation to assess
tumor growth control. We further investigated the
therapeutic effect of FAS modulation by silencing FAS in radiation-responsive
tumors and injecting FAS agonist antibody into radiation-resistant
tumors. Exposure to radiation inhibited MCF7, and to a lesser extent HCC1954
tumor growth in a dose-dependent manner. In contrast, SUM159
tumors were resistant to radiation. The estimated TCD50 values were 19.3 Gy for MCF7 and 44.9 Gy for SUM159. Radiation induced FAS expression in MCF7
tumors, but not SUM159
tumors. We found that silencing of FAS did not negatively impact radiation response in MCF7
tumors, possibly due to compensation by other apoptotic pathways. On the other hand, FAS activating antibody in combination with
radiation treatment delayed SUM159 and HCC1954
tumor growth. However, it did not reach statistical significance compared to
radiation treatment alone. Our results suggest that there is intrinsic variation in radiation response among
breast cancer subtypes. FAS activation concurrent with radiation slows
tumor growth in the radiation-resistant subtypes, but the effect was not significant. Alternative subtype-specific modulators of radiation response are under investigation.