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

Purpose: 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 recepto r correlated with local relapse in early-stage breast cancer patients. In t his communication, we investigated the role that this receptor/ligand pair plays in modulating cellular responses to ionizing radiation in a mammary e pithelial cell line HC11. Methods and Materials: The radiosensitivity of HC11 clonal cells transfecte d to overexpress either the wild-type CSF-1 receptor or CSF-I receptor muta ted at one of the two major autophosphorylation sites (TYR --> PHE 807 or T YR --> PHE 721) was quantitated by standard in vitro clonogenic assays. Results: We demonstrated that a signal transduction pathway regulated by th e phosphorylation of TYR-807 of CSF-1 receptor appears to play a major role in controlling the radiosensitivity of murine mammary epithelial cells. Conclusions: Our observations offer insights into potential pharmacologic a nd gene-therapeutic approaches for the modification of radiation response o f mammary neoplasms. (C) 1999 Elsevier Science Inc.