Signal transduction pathways regulated by CSF-1 receptors modulate the in vitro radiosensitivity of mammary epithelial cells.

Abstract

CSF-1 and its receptor have both been previously implicated in the basic biology and clinical course of mammary and female reproductive tract neoplasms. A recent study (1) demonstrated that expression of this receptor correlated with local relapse in early-stage breast cancer patients. In this communication, we investigated the role that this receptor/ligand pair plays in modulating cellular responses to ionizing radiation in a mammary epithelial cell line HC11. The radiosensitivity of HC11 clonal cells transfected to overexpress either the wild-type CSF-1 receptor or CSF-1 receptor mutated at one of the two major autophosphorylation sites (TYR-->PHE 807 or TYR-->PHE 721) was quantitated by standard in vitro clonogenic assays. We demonstrated that a signal transduction pathway regulated by the phosphorylation of TYR-807 of CSF-1 receptor appears to play a major role in controlling the radiosensitivity of murine mammary epithelial cells. Our observations offer insights into potential pharmacologic and gene-therapeutic approaches for the modification of radiation response of mammary neoplasms.