GSE211290
Novel RXR agonists differentially regulate gene transcription in mammary tumors of MMTV-neu mice
RXR agonists, which activate the RXR nuclear receptor, are effective in multiple preclinical cancer models for both treatment and prevention. While RXR is the target of these compounds, the downstream effects on gene expression differs between compounds. To elucidate the effects of the novel RXR agonist MSU 42011 on the transcriptome in tumors of MMTV-Neu mice, we performed RNA sequencing. For comparative analysis, RNA sequencing was also performed on tumors treated with the FDA approved RXR agonist bexarotene. Female MMTV-Neu mice with established mammary tumors 4 mm in diameter were fed control diet, bexarotene (100 mg/kg in diet), or MSU 42011 (100 mg/kg in diet) for 10 days. Both treatments differentially regulated cancer-relevant gene sets, such as focal adhesion, extracellular matrix, and immune pathways. Many of the top genes differentially regulated by RXR agonists are positively associated with survival in breast cancer patients. While MSU 42011 and bexarotene act on many common pathways, these experiments coupled with gene expression analysis of tumors treated with another novel RXR agonist V-125 highlight the differences in regulation of gene expression between these compounds of the same class. Exploration of these unique effects on gene transcription may lead to an increased understanding of the complex biology behind RXR agonists, and how the activities of this diverse class of compounds can be utilized to treat cancer. Overall design: Comparative gene expression profiling analysis of RNA-seq data for murine tumors treated with different RXR agonists