122 7 Prospective
Because of BRCA1 mutation-coupled ERα−, the cellular level of estradiol
must be raised in breast cancer cells. Such an extremely higher estradiol level can
derive the generation of many hydoxylated products that are able to induce high
frequent genetic mutations (Savage et al. 2014 ). Naturally, BRCA1 is responsi-
ble for repairing the damage of double-strand breaks on DNA. In normal condi-
tions, estrogen can exert an anti-inflammatory role via binding to ERα (Morselli
et al. 2014 ). So it is logically reasonable that the dual alteration of Brca1 mutation
with ERα− could predispose the tumorigenesis/carcinogenesis due to high-level
estrogen-mediated DNA damage, and the lack of anti-inflammatory effects that
are conferred by the estrogen-ERα signaling should exacerbate the inflammatory
lesions from metabolic hypoxia and Warburg effects.
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