The role of the mineralocorticoid receptor (MR) in salt and water balance is well established. What remains less clear is its role in non classical tissues. Recently, we identified the MR as a discriminator between normal human breast, ER positive (ER+) and ER negative (ER-) breast cancers; their loss in breast cancer argues for a role of the MR as a “tumour suppressor”. To investigate the hypothesis that the MR plays a central role in breast biology, perhaps as a receptor for progesterone, we established a colony of mammary tissue-specific MR-null mice.
A mammary tissue-specific MR-null mouse was generated by crossing MMTVcre mice (provided by Prof Jane Visvador, WEHI) with our MR floxed mice. Breeding proceeded normally and gave rise to litters of healthy pups with the expected Mendelian ratios. Mammary tissue (4th inguinal glands) was collected from null mice and littermate controls at 8 weeks of age for histological analyses. Mammary tissue was fixed with Carnoy’s for whole mount analysis and formalin for MR immunohistochemistry. Formal confirmation of the knockout will be provided by MR immunohistochemistry using an MR-specific mouse monoclonal antibody. These studies will be the first to localise MR protein to cells within the mammary tissue of mice; we are currently optimising the protocol. At 8 weeks of age the knockout mammary tissue was poorly developed relative to controls as indicated by reduced branching and overall length, supporting a role for the MR in mammary development.
Studies to investigate additional developmental time points and the role of the MR in mammary tissue during pregnancy and lactation are ongoing. Data collected from these studies may provide the basis for the development of novel treatments/therapies for breast cancer.