Cytotoxicity of 125I-oestrogen decay in non-oestrogen receptor-expressing human breast cancer cells, MDA-231 and oestrogen receptor-expressing MCF-7 cells.
OBJECTIVE
To compare the cytotoxicity of 125I-oestrogen (E-17alpha[125I]iodovinyl-11betamethoxyoestradiol or 125IVME2) decay accumulation in human breast adenocarcinoma cells that do not express oestrogen receptor (ER) (MDA-231 cells) with human breast adenocarcinoma cells that do express ER (MCF-7 cells).


METHODS
MDA-231 cells were labelled with 125IVME2 or [125I]iododeoxyuridine (125IdU), frozen for decay accumulation, thawed and then plated for colony formation. gamma-irradiation survival was also determined. A whole-cell 3H-oestrogen-binding assay and a specific-binding assay were used to detect ER.


RESULTS
No MDA-231 cell killing by accumulated 125IVME2 decays (up to 440 dpc) was observed but ER-positive MCF-7 cells were killed by 125IVME2 (D(o)=28 dpc). MDA-231 cells were not significantly more radioresistant to gamma-rays (D(o)=1.7Gy for MDA-231 cells; 1 Gy for MCF-7 cells) or to 125IdU decays (D(o)= 44dpc for MDA-231 cells; 30 dpc for MCF-7 cells). No ER were detected in MDA-231 cells.


CONCLUSIONS
ER-negative cells, MDA-231, are not killed by 125IVME2 decay accumulation. It is speculated that without ER (required to translocate the 125IVME2 to its nuclear target), formation of the 125IVME2-ER-DNA oestrogen-response element (ERE) complex and subsequent specific irradiation of the DNA at the ERE cannot occur. These results support the hypothesis that the nuclear genome is a critical target for radiation-induced cell death.
Yasui
L S
LS
Northern Illinois University, Department of Biological Sciences, DeKalb, IL 60115, USA. lyasui@niu.edu
Hughes
A
A
Desombre
E R
ER
D001943:Breast Neoplasms / Q000532:radiotherapy*; D002470:Cell Survival / Q000528:radiation effects; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D005720:Gamma Rays; D006801:Humans; D007065:Idoxuridine / Q000378:metabolism; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D011836:Radiation Tolerance; D011960:Receptors, Estrogen / Q000032:analysis*; D014407:Tumor Cells, Cultured
D004967:Estrogens; D007457:Iodine Radioisotopes; D011960:Receptors, Estrogen; D007065:Idoxuridine