The short-chain dehydrogenase/reductase (SDR) super family of oxidoreductase enzymes perform a large array of metabolic processes regarding metabolism of fatty acid derived endocrine hormones. They play important roles in both biosynthesis and regulation of fatty acids, retinoids and cholesterol derived hormones and regulate ligand/receptor interactions within the cell. Two well characterized family members outline the importance of this diverse protein family. HSD11B1 and HSD11B2 are important in the regeneration, activation and inactivation of a potent endocrine hormone, cortisol. Loss of either genes can result a diseased state and have been characterized to play fundamental roles in the development of lung abnormalities, type II diabetes and apparent mineralocorticoid excess (AME) syndrome.  Despite the importance of SDR family members the SDR protein family remains poorly characterized.  

SDR family members have been associated with many metabolic based disorders. In addition, many cancers have shown either up or down-regulation of SDR family members and further instances of mutations and copy number variations have been shown within several SDR genes. Given the extent of their metabolic capabilities on many substrates that are of great importance to cellular homeostasis it is not surprisingly that several of the family members are linked to cancer growth, progression and metastasis. We have characterized a group of six SDR family members predominantly in mice in relation to mRNA expression levels and protein localisation. Furthermore, expression profiling of several well characterized endocrine responsive cancers including prostate, colon and breast derived cancer cells lines assessed for mRNA and protein expression and further analysis of downstream signalling pathways linked to SDR’s.

Expression analysis of several cancer cell lines shows SDR family members as potential regulators of cell signalling processes in cancer cells that help drive progression and metastasis and recent interest in SDR targeted inhibitors may provide a possibility of target cancer treatment for further clinical use.