Polyphosphate Affects on Breast Cancer Cell Survival

Abstract

Abstract : The research supported by the Department of Defense Breast Cancer Research Program (BCRP) studies whether the polyphosphate survival function is conserved between prokaryotes and eukaryotes and specifically whether polyphosphates are involved in the increased survival of breast cancer cells. While in the process of developing modified MCF-7 breast cancer cells, an exciting opportunity arose to investigate polyphosphates and their effect on DNA damage response. It is well documented that DNA damaging agents can cause genomic instability and lead to various forms of cancer including breast cancer. Without proper cell cycle checkpoints that trigger repair of the damage or induction of apoptosis, genetic mutations can be propagated, possibly initiating tumorigenesis. Functional analysis of DNA damage response, cell cycle checkpoints which involve BRCA1, genome integrity, and tumor evolution will build the knowledge of the mechanisms involved in breast cancer. The principle investigator ceased this opportunity to study polyphosphates and DNA damage response with respect to cell survival and DNA repair mutagenesis and the DNA damage response (SOS response) which follows extensive DNA damage. It has been discovered that: Loss of polyphosphates increase the cells ability to survive UV radiation; The decrease in survival is not limited to DNA damage caused by UV; The decrease in survival is not specific to the loss of a specific DNA repair mechanism; Polyphosphate levels transiently increase after UV irradiation, in a time frame consistent with error-prone DNA repair; Polyphosphates influence cell survival in pathways separate from RecA and Pol V; and Pol IV functionality in cell survival requires polyphosphates to directly or indirectly instigate the Pol IV pathway.