Hypoxanthine phosphoribosyl transferase 1 is upregulated, predicts clinical outcome and controls gene expression in breast cancer

Hypoxanthine phosphoribosyl transferase 1 (HPRT1) is traditionally believed to be a housekeeping gene; however, recent reports suggest that it is upregulated in several cancers and associates with clinical outcome. Like several cancer testis (CT) genes, HPRT1 is found on chromosome X, and encodes the HPRT enzyme, which functions in recycling nucleotides to supply for DNA and RNA synthesis in actively dividing cells. Here, we have used genome wide expression to interrogate its expression across all known cancer types and elucidated its functional role in breast cancer. We observed elevated HPRT1 RNA levels in malignant tissues when compared to normal controls, indicating its potential as a diagnostic and prognostic marker. Further, in breast cancer, subtype specific analysis showed that its expression was highest in basal and triple-negative breast cancer, and HPRT1 knockdown in breast cancer cells suggested that HPRT1 positively regulates genes specific to cellular and DNA repair pathways. Collectively, our results essentially highlight the importance and change the way HPRT1’s function is studied in biology, and warrants careful examination of its role in cancer. HPRT1 was knocked down using two distinct siRNA oligos in three cell lines, MCF-10A (immortalized mammary epithelium), MCF-7 (Estrogen receptor positive breast cancer cell line), MDA-MB-231 (Estrogen receptor, progesterone receptor and HER2 negative breast cancer cell line)