Role of Epimorphin and Progesterone in Breast Development
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: The mammary gland is a specialized organ in mammals that undergoes distinct stages of development in order to perform a vital function for offspring; milk production. The epithelial cells, which produce milk, must receive proper signals from hormones in the blood, nearby cells and components of its microenvironment to acquire this function. Before epithelial cells can produce milk, they must develop into lobuloalveoli (functional units) through morphogenesis, a process that involves proliferation, invasion and structural changes. Breast cancer happens when signals for normal morphogenesis go awry, epithelial cells grow in a disorderly and uncontrolled manner. Epimorphin is a morphogenic signal that when overproduced in mice causes lobuloalveolar structures to develop prematurely and excessively.
 
 
 
 
 
 
 
 By determining how microenvironmental signals like epimorphin control normal development, insight will be gained to the mechanisms that lead to abnormal signals that cause cancer. The specific type of morphogenesis that epimorphin plays a role in is the development of branched structures and of milk producing structures called lobuloalveoli. Progesterone, a hormone that circulates in the blood, binds to targets in epithelial and surrounding cells called progesterone receptors and also directs epithelial cells to branch and to develop into lobuloalveoli. I hypothesize that epimorphin and progesterone/progesterone receptor stimulate epithelial morphogenesis through a common pathway or through two separate pathways that collaborate in these developmental processes.
 
 
 
 
 
 
 
 To determine if a relationship exists between epimorphin and progesterone/progesterone receptor in mammary morphogenesis, I will conduct experiments with mammary epithelial cells in culture and mammary glands in live mice. Quantification of these molecules will be done using standard molecular biology techniques. Mice that overproduce epimorphin in their mammary glands will be used along with normal mice to determine if progesterone receptor levels are increased by epimorphin. To determine if progesterone can regulate the production of epimorphin, I will treat epithelial cells that normally produce epimorphin with progesterone and determine if epimorphin levels increase compared to non-treated cells. I will also test whether progesterone treatments in ovariectomized mice increase the level of epimorphin. 
 
 
 
 
 
 
 
 To understand the anomalous behavior of breast cancer cells, the signals that cause deviations from normal developmental programs must be determined. Many of the inappropriate signals are the same ones that control normal development except that they are misregulated. This study will focus on the dynamic information that cause the specialized milk producing cells, the lobuloalveoli, to develop in the normal breast and how these same signals become disrupted in breast cancer.