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


METHODS
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.


RESULTS
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.


CONCLUSIONS
Our observations offer insights into potential pharmacologic and gene-therapeutic approaches for the modification of radiation response of mammary neoplasms.
Kacinski
B M
BM
Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06520-8040, USA.
Rodov
S
S
Sapi
E
E
D000818:Animals; D002460:Cell Line / Q000528:radiation effects; D003114:Colony-Forming Units Assay; D005260:Female; D008321:Mammary Glands, Animal / Q000166:cytology / Q000528:radiation effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D011836:Radiation Tolerance / Q000235:genetics / Q000502:physiology*; D011853:Radiobiology; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D014162:Transfection
D016186:Receptor, Macrophage Colony-Stimulating Factor