Estrogen receptor status is a diagnostic parameter in
breast cancer treatment.
Estrogen receptor presence is related to a better prognosis because the principal treatments attacking
breast cancer tumors have their action site directed at the
estrogen receptor. However, the two different subtypes of
estrogen receptor, ERα and ERβ, have different functions. In this work an alternative point of view focusing on oxidative stress is shown, given that
estrogen receptors regulate several
proteins related to this oxidative stress, such as
antioxidant enzymes,
sirtuins, and
uncoupling proteins. Postmenopausal human
breast tumors with different ERα/ERβ ratios were analyzed to characterize the amount of oxidative stress, mitochondrial function, and proliferation-related and oxidative stress-activated signaling pathways. Results showed that
tumors with a low ERα/ERβ ratio have greater oxidative damage and higher
antioxidant enzyme protein levels, as well as
uncoupling protein (UCP) and
sirtuin 3 (
SIRT3), and have high studied signaling pathway activation.
Glutathione peroxidase,
Complex V,
Complex III, Complex II, Complex IV, AKT, SAPK, and ERα were significantly and positively correlated with ERα/ERβ ratio. However, carbonyl groups,
catalase, CuZn-
superoxide dismutase, UCP5,
SIRT3, and ERβ were significantly and negatively correlated with ERα/ERβ ratio. From the independent variables included in the step-by-step stepwise multiple linear regression analysis, only the ERα/ERβ ratio was independently associated with carbonyl groups. Surprisingly, these low ERα/ERβ ratio
tumors have poor prognosis for the patient, and these results and those of other authors suggest that these
tumors are adapted to conditions of increased oxidative stress.