Mammary gland development involves complex interactions among steroid hormones and growth factors, and knockout experiments have demonstrated essential roles for estrogen receptors (ER) and progesterone receptors (PR) in this process. Recent in vitro data indicate that metastasis-associated protein 1 (MTA1) interacts with ERα and inhibits ER transactivation, but its in vivo role is not known. Bagheri-Yarmand et al.()investigated the in vivo role by expressing MTA1 under the control of a mouse mammary tumour virus promotor. The mammary glands of virgin transgenic mice had estrogen-independent ductal branching, produced pregnancy-dependent milk proteins and showed increased proliferation of alveolar epithelial cells. Furthermore, MTA1 dysregulation in mammary epithelium triggered an imbalance of PR isoforms, downregulating isoform PR-B and upregulating isoform PR-A. The PR-A targets cyclin D1 and Bcl-XL were also upregulated, raising the interesting possibility that Bcl-XL was responsible for the formation of the breast nodules and breast tumours seen in many of the transgenic individuals. This study establishes for the first time a role for MTA1 in mammary gland development and tumourigenesis, and provides an in vivo model with which to identify additional novel targets of MTA1.
