Gene expression profiling distinguishes between spontaneous and radiation-induced rat mammary cancers

Abstract

[Background] Low dose radiation risk is difficult to assess because expected excess cancer incidence is much smaller than the background, spontaneous incidence. It is hence anticipated that information of molecular characteristics of radiation-associated cancers would aid to improve low dose risk assessment by distinguishing radiogenic cancers from spontaneous ones. We aimed to distinguish between them by means of gene expression profiling method in rat mammary cancer.
[Method] Female rats were either irradiated with 1 Gy of gamma rays or left untreated. Mammary adenocarcinomas and normal mammary tissues were subjected to microarray analysis (Affymetrix GeneChip®; ~30,000 probe sets). Total RNA was extracted for labeled cRNA synthesis, followed by hybridization to microarrays and scanning. Real-time RT-PCR was performed for selected genes which showed differential expression.
[Result and Conclusion] Hierarchical cluster analysis separated a single cluster of spontaneous carcinomas, whereas radiation-induced cancers were heterogeneous and did not form a single cluster. We extracted 66 genes that showed differential expression between the two etiological groups, based on fold difference and P values of t-test. Real-time RT-PCR analysis on selected genes confirmed that 14 genes showed differential expression even after new tissue samples were included. These results strongly support the possibility to distinguish between radiogenic and spontaneous cancers based on gene expression and suggest a difference between their mechanisms of development.