The Role of a Newly Discovered Neuregulin 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: A number of protein factors and hormones affect the growth, survival and progression of breast cells from a normal to a malignant state. Our work focuses on finding molecules related to the molecule, neuregulin, which is known to activate the ErbB2 receptor that is expressed in roughly one-fourth of all human breast tumors. We believe that it is important to identify these molecules as their activities could affect the development of breast cancer and influence the growth rate of malignant cells. 
 
 
 
 
 
 
 
 We have identified a candidate novel neuregulin, AA238077, through a search of the databases that contain the DNA sequences of many genes of unknown function. When the sequence of AA238077 is compared with collections of known genes, it is most closely related to two of the previously identified distinct neuregulin genes, neuregulin-1 and neuregulin-3. While this similarity suggests that it too is a neuregulin, we must test its ability to activate ErbB2 and the related receptors ErbB3 and ErbB4 before its identity as a neuregulin-like molecule can be confirmed. We will accomplish this by first preparing the AA238077 protein in the laboratory and testing the ability of this protein to stimulate the activity of these receptors. Many breast cancer cells express one or more of the four ErbB receptors and we will use a set of tumor cell lines to assess the activity of AA238077. 
 
 
 
 
 
 
 
 The ability of neuregulin-1 to bind to breast cancer cells is currently being exploited as a way to target the specific destruction of ErbB2-expressing tumors. The general strategy is to couple a toxic substance to the neuregulin-1 molecule so that the breast tumor cells will be preferentially destroyed because they express more ErbB2 and other ErbB receptors than normal cells. Our previous identification and characterization of neuregulin-2 suggests that it binds to and activates certain breast cancer cells better than neuregulin-l. This suggests that each of the neuregulins, and perhaps AA238077, could be separately used to target different tumor populations. In addition, as it has been observed that neuregulin-1 can inhibit the ability of some breast cancer cells to divide, the distinct signaling properties of each of the neuregulins holds the promise that they may be useful to control the growth of different sets of breast tumors. Lastly, on a very practical level, it is important to know if any of the neuregulins is expressed (detectable) in the normal or cancerous breast as therapeutic strategies designed involving the use of these molecules could be affected by the presence of an as yet unidentified neuregulin-like molecule. 
 
 
 
 
 
 
 
 In order to best design therapies directed against breast cancer, it is important to identify as many of the molecular players involved. Although a complete understanding will certainly take many more years, we are in a position to make significant progress in finding the molecules that activate ErbB2 and the related receptors ErbB3 and ErbB4.