P1-04-06: Ionizing Radiation Reprograms Non-Tumorigenic Cancer Cells into Cancer Stem Cells.

Abstract Breast cancers are thought to be organized hierarchically with a small number of breast cancer stem cells (BCSCs) able to re-grow a tumor while their progeny lack this feature. BCSCs in breast cancer have been found to be relatively resistant to radiation and several groups reported enrichment for BCSCs when breast cancers are subjected to classical anticancer treatment. Differentiation of BCSCs is thought to be unidirectional but an alternative model assumes that stemness can be obtained by clonal evolution. In this study, we quantified the number of BCSCs surviving after radiation treatment. We compared the number of surviving BCSCs to the expected number and found an increase in BCSCs after irradiation that could not be explained by current models. We propose that radiation induces a BCSC phenotype in previously non-BCSCs and show that this transition is Notch-dependent and coincided with up-regulation of the transcription factors Oct4, Sox-2, Nanog, and Klf4. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-04-06.