Expression of oestrogen receptor and transforming growth factor-alpha in MCF-7 cells after exposure to fractionated irradiation.
The expression of critical growth controlling genes was studied in MCF-7 cells after exposure to cumulative radiation doses of 20 and 60 Gy yielding cell lines called MCF-IR-1 and MCF-IR-3, respectively. The irradiated cell lines exhibited increased plating efficiencies but no differences in growth rates. MCF-IR-1/-IR-3 cells showed a reduced oestrogen responsiveness as indicated by their diminished response to tamoxifen-induced growth arrest and 17 beta-oestradiol (E2)-induced growth stimulation. The reduced expression of oestrogen receptor (ER) was determined by quantitative immune peroxidase staining of single cells and by total cellular E2 binding. There was also a radiation dose-dependent increase in the radiosensitivity of MCF-IR-3 cells as determined by the radiobiological parameters alpha, beta, and D (mean inactivation dose). Using RNA protection assays the irradiated cell lines produced steady-state ER mRNA at reduced levels while the levels of TGF-alpha were unchanged in MCF-IR-1 cells but increased 2.8-fold in MCF-IR-3 cells. A similar pattern was seen for TGF-alpha protein. While the current analyses cannot differentiate between radiation-induced altered gene expression or cell selection the results demonstrate that reduced ER expression and increased TGF-alpha expression are associated with the survival of MCF-7 cells after fractionated irradiation in vitro. In contrast, the MCF-IR cells were found to be more radiosensitive in acute survival experiments.
Department of Radiation Oncology, Medical College of Virginia, Richmond 23298-0058.
R K
RK
Schmidt-Ullrich
K
K
Valerie
W
W
Chan
D E
DE
Wazer
P S
PS
Lin
D001943:Breast Neoplasms / Q000235:genetics*; D002460:Cell Line; D002470:Cell Survival / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D005260:Female; D015870:Gene Expression; D006801:Humans; D011960:Receptors, Estrogen / Q000235:genetics*; D015291:Transforming Growth Factors / Q000235:genetics*; D014407:Tumor Cells, Cultured / Q000528:radiation effects*
D011960:Receptors, Estrogen; D015291:Transforming Growth Factors