Intracellular redox regulation on hormone-dependent proliferation of breast cancer

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In this study, we obtained following results :1)By subcloning a breast cancer cell line, MCF-7, we revealed the subclones which expressed low level of intracellular thioredoxin (TRX) grew faster than those with high lever of TRX expression.2)Immunothistochemical analysis of tumor tissues of breast cancer patients showed that. in high intracellular TRX expression group, the estrogen receptor (ER) activity significantly related to the expression of pS-2. However, no relationship between ER activity and pS-2 expression in low TRX group. Moreover, p53 positive rate also related to mitotic index of tumor tissues in former group.3)In wild type p53 positive breast cancer cell line, p53-dependent p21 transcription activity was enhanced by TRX gene transfection.4)Analysis using mutant of ER (cystein to alanine) revealed that not only DNA-binding site but also legend binding region had high sensitive part to redox regulating by TRX.5)Redox factor1 (Ref-1) which is transcription factor related to redox regulation was mainly expressed as reduced type in uterine leiomyoma cells, and expressed as oxidised type in uterine smooth muscle. On the other hand ,TRX was expressed as oxidised type in uterine leiomyoma, and was expressed as reduced type in uterine smooth muscle.These results suggest that redox regulation on ER is important for biological activity of breast cancer, and that hormone therapy relating ER must be considered by the molecular mechanism of ER regulation.