Control of the Mammary Cell Cycle Clock by Estrogen and Progesterone
Abstract
Both the growth and the development of the mammary gland are controlled by the female hormones estrogen and progesterone, and by interactions between the epithelial and stromal compartments of the breast. Changes in the regulation of any of these processes may lead to breast cancer. Therefore, we need to understand in detail the mechanisms that control proliferation and development of the mammary gland. We have investigated the role of progesterone in the process of sidebranching and alveologenesis In the mammary gland using mice laclting the progesterone receptor which are defective in these processes. By reconstituting murine mammary glands in vivo, we have shown that the progesterone receptor is required only in epithelial cells for proper sidebranching to occur. Our studies suggest that progesterone acts in a paracrine manner and more recent data suggests that Wnt-4 is a possible mediator of this paracrine effect. In parallel studies, we have observed that breast cancer cells can dramatically downregulate the expression of hepatocyte growth factor in cocultured libroblasts. These results suggest an important role of paracrine interactions also in breast cancer development. In addition, we have characterized the role of the estrogen receptor in regulating the proliferation of breast cancer cells. We postulate that the ability of estrogen receptor to control cyclin Dl expression and proliferation of breast cancer cells may be acquired during breast cancer development. In conclusion, we have studied the role of female hormones and stroma-epithelial interactions in regulating mammary gland development and tumorigenesis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 1999
- Accession Number
- ADA391255
Entities
People
- Robert Weinberg
Organizations
- Whitehead Institute