Gene Expression Profiling of MCF10A Breast Epithelial Cells Exposed to IOERT

Intraoperative electron radiation therapy (IOERT) is a therapeutic approach that delivers a single high dose of ionizing radiation (IR) directly to the tumor bed during cancer surgery. The main goal of IOERT is to counteract tumor growth by acting on residual cancer cells as well as to preserve healthy surrounding tissue from the side-effects of radiation therapy. The radiobiology of the healthy tissue response to IR is a topic of interest which may contribute to avoiding impairment of normal tissue and organ function and to reducing the risks of secondary cancer. The purpose of the study was to highlight cell and gene expression responses following IOERT treatment in the human non-tumorigenic MCF10A cell line in order to find new potential biomarkers of radiosensitivity/radioresistance.

Gene-expression profiling of MCF10A cells treated with 9 and 23 Gy doses (IOERT boost and exclusive treatment, respectively), was performed by whole-genome cDNA microarrays. Real-time quantitative reverse transcription (qRT-PCR), immunofluorescence and immunoblot experiments were carried out to validate candidate IOERT biomarkers. Clonogenic tests and morphological evaluations to examine cellular effects induced by radiation were also conducted.

The study revealed a dose-dependent gene-expression profile and specific key genes that may be proposed as novel markers of radiosensitivity. Our results show consistent differences in non-tumorigenic cell tolerance and in the molecular response of MCF10A cells to different IOERTs. In particular, after 9 Gy of exposure, the selection of a radioresistant cell fraction was observed.

The possibility of clarifying the molecular strategies adopted by cells in choosing between death or survival after IR-induced damage opens-up new avenues for the selection of a proper personalized therapy schedule.