Molecular investigation of Breast Cancer xenograft model exposed to proton radiations

Specific Breast Cncer (BC) subtypes are associated with a bad prognosis due to the absence of successful treatment plans. Moreover, the triple negative breast cancer (TNBC) subtype, with estrogen (ER), progesterone (PR) and human epidermal growth factor-2 (HER2) negative receptors status, were characterized by unsuccessful therapies, makes it a clinical challenge for oncologists. In addition, Proton RadioTherapy (PRT) represents an effective treatment also against conventional radiotherapy (RT) resistant cancers, and a promising therapeutically choice for TNBC. Our study aimed at analyze the in vivo molecular response induced by PRT in a MDA-MB-231 triple negative Breast Cancer xenograft model, focusing on gene expression profile (GEP) analyses. Our results demonstrate the multiple advantages of xenograft tissue microarrays for preclinical signature characterization of PRT to understand the molecular mechanism activated and to discover new molecular targets. Proton-induced gene expression changes in MDA-MB-231 Breast Cancer xenograft model after 2, 6 and 9Gy of IR doses, were analyzed as two-color hybridizations using Agilent Technologies whole human genome 4x44K microarrays. Samples were named as follow: MDA-MB-231 xenograft mouse exposed to 2Gy PRT; MDA-MB-231 xenograft mouse exposed to 6Gy PRT; MDA-MB-231 xenograft mouse exposed to 9Gy PRT.