Pathway-Specific Gene Expression in Breast Cancer Cells
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 identification of the genes involved in breast tumor progression will be necessary to understand the disease and for the establishment of novel drug targets and therapies. Much effort has gone into finding genetic defects or mutations associated with cancer. However, in breast cancer it appears that defects in hereditary genes, such as BRCA1 and BRCA2 account for only about 10% of total incidence. Thus, sporadic breast cancer is associated with newly-produced genetic defects that occurs only in the tumor cells. While information on tumor suppressors (e.g. p53) and oncogenes (e.g. Her-2) are very helpful in categorizing breast cancer, there remains a huge 'black box' of genetic defects with no defined association with the key clinical properties of the disease. Because of the many sub-types of clinical breast cancer, it appears that complex associations of genetic defects as well as subtle changes in the amounts of normal genes are both involved. Until recently, the role of specific genes and their products has been carried out largely on a one-gene-at-a-time basis. New methods, however, permit simultaneous profiling of the expression of thousands of genes in tumor samples. This provides information on the amounts of gene products present (i.e. RNA or gene duplication) and the absence of gene products (i.e., mutation or gene loss). Results from such studies indicate that there are hundreds of gene expression differences between normal breast tissue and tumors. 
 
 
 
 
 
 
 
 In this project we plan to elucidate genes critical to breast cancer progression. We will focus on those genes associated with known cellular growth, survival and motility pathways. In other words, the pathways that underlie the clinical issues of cancer proliferation, resistance to cell death and drug treatment, and spread in the body (metastasis). The two protein signaling pathways of particular interest to us are the ras/Erk pathway, which has been implicated in tumor cell proliferation; and the PI3-kinase/Akt pathway, which has been implicated in tumor cell survival and motility. Our plan is to genetically modulate these two pathways by introducing blocking genes into breast cancer cells. These artificially mutated cells gain many of the characteristics of tumor cells. We can confirm these properties using biological (e.g. motility assays) and biochemical/genetic tests. Then, we can make extracts from the cells and use special 2,000 gene cDNA arrays to assay for the presence and changes in amounts of all known cancer-associated genes. The list of genes to be analyzed includes those involved in cell growth, cell division, and invasion processes. We can also use commercially available arrays (Affymetrix) to expand and confirm the data we obtain using our custom-made cancer cDNA arrays. In other experiments we can use specific drugs to modulate ras/Erk and PI3-kinase/Akt and determine the effect on the breast cancer cells' genetic profile. 
 
 
 
 
 
 
 
 These studies will result in a very large data set of pathway-specific gene targets that will be made publicly available to the breast cancer and broader scientific communities through the worldwide web. It is anticipated that the data set will include many genes known to be involved in breast tumor progression, and many more that have not been previously implicated. The identification of novel genes involved in breast cancer progression is anticipated to spawn an array of studies directed toward assessing the utility of such genes as targets for anti-cancer therapies.