Estrogen receptor-interacting proteins in breast cancer
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 normal development and function of the breast is regulated by a number of hormones including estrogen. Among other effects, estrogen stimulates many cells of the breast tissue to proliferate, i.e. to replicate themselves. Many breast cancer cells also require estrogen to stimulate their growth, and for this reason, drugs that block the action of estrogen are often used effectively in therapy of breast cancers. However, some breast cancers do not respond to these anti-estrogen therapies and, in addition, many breast cancers that initially respond to anti-estrogen therapy eventually become resistant. For these reasons, it is important to continue seeking new methods of treatment. The ability to design new treatments will depend upon our ability to understand the nature of cancer cells and how their growth is stimulated and regulated. Because estrogen remains a central factor in stimulating breast cancer cell growth, we are endeavoring to gain a more detailed understanding of the mechanism of estrogen action, since this knowledge will be essential for designing new therapeutic strategies to block estrogen stimulation of breast cancer cell growth.
 
 
 
 
 
 
 
 Estrogen stimulates breast cancer cell growth by activating specific genes in breast cells that are responsible for cell growth and division. Much is known about this mechanism already. The hormone estrogen enters the cell and binds tightly to a specific protein, the estrogen receptor. The binding of the hormone activates the receptor, which then binds to specific genes in the cell nucleus and activates those genes. Some of these activated genes are responsible for stimulating cell growth. Why and how the binding of the estrogen receptor to specific genes activates those genes is still not known, and a better understanding of this phenomenon is the major goal of this proposed investigation. In order for the estrogen receptor to activate the genes that it binds to, it is believed to require assistance from other, as yet unknown, proteins in the cell. In our preliminary work, we have identified several novel proteins that interact with the estrogen receptor in a very specific manner: these novel proteins bind to the receptor only after the receptor has been activated by hormone; furthermore, they appear to interact with a specific portion of the receptor that is known to be important for the receptor’s ability to activate the target genes. It is our hypothesis that these proteins play important roles in the action of the estrogen receptor. We therefore propose to identify these proteins and to determine the nature of their roles in assisting the estrogen receptor to activate specific genes in breast cancer cells.
 
 
 
 
 
 
 
 These novel proteins may represent novel targets for breast cancer therapy, since blocking their action may prevent the growth of some tumors that do not respond to antiestrogen therapy. Furthermore, combination therapy, involving anti-estrogens and agents that block the action of these novel proteins, may prevent the recurrence of some breast tumors. More basic knowledge of how estrogen activates genes is essential before such novel therapies can be designed, and such knowledge is the goal of this proposal.