PTHrP regulates fatty acid metabolism via novel lncRNA in breast cancer initiation and progression models

The 5-year survival rate for women with metastatic breast cancer is 29%. Potential biomarkers identification is important for new therapeutic treatment in affected patients. Previous studies have shown that Parathyroid hormone-related peptide (PTHrP) plays a critical role in breast cancer growth and metastasis. The aim of our study was to use a genetically modified breast cancer mouse model to precisely examine the role of PTHrP from early primary breast cancer initiation to late progression. We identified a novel lncRNA, a new target for fatty acid metabolism that can be regulated by PTHrP in our unique mouse breast cancer model. We confirmed that a potential human lncRNA, OLMALINC, plays a similar role in fatty acid metabolism that can be regulated by PTHrP. Therefore, we validated our mouse finding in the human breast cancer cell lines. Genetically engineered mouse models provide valuable tools to study the molecular progression for breast cancer metastasis. Here we generated Pthrpflox/flox; Cre+ mT/mG and Pthrpwt/wt; Cre+ mT/mG tumor and tumor-free mice to examine the signaling pathways under the control of PTHrP from early to late stage of tumorigenesis. GFP+ mammary epithelial cells were further enriched for subsequent RNA sequencing (RNAseq) analyses.