ALTERED EXPRESSION OF EPIDERMAL GROWTH-FACTOR RECEPTOR AND ESTROGEN-RECEPTOR IN MCF-7 CELLS AFTER SINGLE AND REPEATED RADIATION EXPOSURES

Purpose: Studies on radiation-induced changes in gene expression are l ikely to be very important in developing a better understanding of cel lular responses to ionizing radiation. While there is some information on the activation of cellular signal transduction pathways after radi ation, few late reacting target genes have been identified. This study focuses on the characterization of expression modulation of two criti cal growth regulatory genes, estrogen receptor and epidermal growth fa ctor-receptor in malignant mammary epithelial cells in response to sin gle and repeated ionizing radiation exposures. Methods and Materials: MCF-7 cells were used for single radiation exposure (2-50 Gy) experime nts and MCF-IR-3 cells, generated by exposure to cumulative doses of 6 0 Gy in 2 Gy fractions, respectively, were used to study the effects o f repeated exposures. Steady-state messenger ribonucleic acid levels f or estrogen receptor, epidermal growth factor-receptor, and transformi ng growth factor-ct were determined by ribonucleic acid protection exp eriments. Estrogen receptor and epidermal growth factor-receptor prote in expression was quantitated by competitive binding studies with H-3- estradiol and I-125-EGF. Results: MCF-IR-3 cells showed a permanent th ree-fold down-regulation of the estrogen receptor messenger ribonuclei c acid and protein, while epidermal growth factor-receptor was upregul ated about nine-fold. Epidermal growth factor-receptor was substantial ly up-regulated in MCF-7 cells, at both the mRNA and protein levels, w ithin 24 h of a single 2 Gy exposures, while there was a two-fold conc omitant increase in transforming growth factor-alpha messenger ribonuc leic acid expression. A decrease in estrogen receptor messenger ribonu cleic acid and protein was suggested only after higher doses of single radiation exposures. Conclusion: Single and repeated radiation exposu res modulate the expression of two critical growth promoting genes, es trogen receptor and epidermal growth factor-receptor, in MCF-7 cells. The inverse expression of estrogen receptor and epidermal growth facto r-receptor established for estrogen receptor-positive malignant mammar y epithelial cells is maintained in MCF-7 cells after single and repea ted exposures suggesting that radiation acts through common regulatory circuits and may modulate the cellular phenotype.