Characterising transcriptional changes throughout c-MYC-driven tumorigenesis in the mammary gland (MMTV-cMYC mouse model)

c-MYC oncogene is one of the driver lesions in many types of cancer. Among breast cancers, triple negative subtype (TNBC) is characterised by high aggressivness and is associated with high transcriptional activity of MYC. MMTV-cMYC mouse model, in which ectopic expression of c-MYC is driven by mouse mammary tumour virus promoter, is a widely used model of MYC-driven breast cancer. MMTV-cMYC mice develop tumours in the mammary gland(s) at ages ranging from 6 to 10 months. MYC regulates activity of multiple processes including cell cyle, proliferation, metabolism, protein translation, inflammation and apoptosis among others. Previous studies demonstrated that MMTV-cMYC tumours are very heterogeneous. However, how different procecesses regulated by MYC contribute to different steps of the transformation process and tumour development is not known. To evaluate how the expression of genes changes from the initiation of transformation process by ectopic expression of c-MYC in mammary gland epithelial cells to the development of tumours, we perfomed RNAseq analysis of tissues collected from mammary glands and tumours of MMTV-cMYC mice of different ages. Wild type age-matched littermates were used as controls. Overall design: Hyperplastic 6 week and 12 week old mammary glands as well as small (less than 3X3 mm in diameter) and large (10X10 mm in diameter) tumours were colelcted from MMTV-cMYC female mice on FVBN/J background. Normal mammary glands were collected from 6 week old MMTV-cMYC negative littermate controls. This study also aimed to evalute how glucose metabolism changes throughout MYC-induced mammary gland tumorigenesis. Hence all mice received a bolus injection of [U-13C]-glucose i.v. at 570 mg/kg (calculated as 20 mg of [U-13C]-glucose for an average body weight of 35g dissolved in 100 µl of saline). Tissues were snap frozen in liquid nitrogen and ground.