Role of a DNA Damage Response Gene 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: Numerous studies have demonstrated an increased incidence of breast cancer in women exposed to therapeutic and occupational levels of radiation. This radiation mutates cellular DNA, which ultimately leads to breast cancer in these women. However, besides these unusual circumstances, DNA damage occurs continually in all individuals by means of normal metabolic processes, like the breakdown of food into energy. Since damaged DNA is widely considered to be the dominant force in the generation of cancer, the efficiency with which cells protect the integrity of DNA is imperative for the prevention of cancer in all individuals. Consistent with this analysis, the elimination of genes that repair damaged DNA or prevent mutated cells from growing is well correlated with the generation of breast cancer. For example, prognosis is poor for breast cancer patients with tumors that harbor mutations in p53, a protein that normally prevents mutated cells from dividing. In addition, people with mutations in the breast cancer associated genes, BRCA1 and BRCA2, have a 200 fold greater risk of breast cancer. 
 
 
 
 
 
 
 
 We have evidence for the likely involvement of a gene called ATR in responses to damaged DNA. ATR is related to the ATM tumor suppressor gene and is the human equivalent of genes used in other organisms for maintenance of DNA integrity. The similarity of these genes and recent studies indicate that ATR is potentially involved in regulating genes known to be required to prevent mutated cells from multiplying, like p53. In addition, I provide preliminary evidence that further substantiates a link between the function of BRCA1 and ATR. To explore the role of ATR in responses to damaged DNA, I plan to eliminate ATR from fully developed cells. Thus, if ATR is necessary for regulating BRCA1 for example, then when it is eliminated BRCA1 should be unresponsive to damaged DNA. In addition, the method I plan to use to eliminate ATR is novel and would prove useful for studying the function of genes like BRCA1 and BRCA2. Finally, I have an experimental strategy to identify yet undiscovered genes that normally function in preventing breast cancer. 
 
 
 
 
 
 
 
 Together, these studies will lead to better prevention and treatment of breast cancer. For example, 80% of all breast cancer is of late onset and late onset breast cancer is often aggregated in families. It is therefore reasonable to hypothesize that genetic predisposition causes the development of breast cancer in these cases. Potential candidates for these genes include molecules that regulate DNA-damage responses like ATR. In addition, knowledge of these mechanisms may not only lead to a better understanding of the predisposition to and prognosis of breast cancer, but also to better treatments. It is conceivable that treatments for breast cancer might one day be formulated and chosen based on the genetic characteristics of both the tumor and the patient. It seems likely that ATR and the molecules it regulates will be among these genes.