First published online June 28, 2004
Development 131, 1404e (2004)
© The Company of Biologists Limited
MTA1 dysregulation in the mammary gland
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 ER
and inhibits ER transactivation, but its in
vivo role is not known. Bagheri-Yarmand et al.
(p. 3469)
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.
Related articles in Development:
- Metastasis-associated protein 1 deregulation causes inappropriate mammary gland development and tumorigenesis
- Rozita Bagheri-Yarmand, Amjad H. Talukder, Rui-An Wang, Ratna K. Vadlamudi, and Rakesh Kumar
Development 2004 131: 3469-3479.
[Abstract]
[Full Text]
