Fig. 8.

A high level of PPP3CA expression is associated with a poor prognosis in patients with luminal A–type breast cancer treated with endocrine therapy or tamoxifen. (A and B) Relapse-free survival according to the expression of PPP3CA (202429_s_at) was determined for patients with different breast cancer types in clinical cohorts acquired from the Kaplan–Meier plotter database. The analysis was performed for patients regardless of the treatment received (A) or for those with luminal A– or luminal B–type breast cancer who received endocrine therapy or treatment with tamoxifen (B). High- and low-PPP3CA expression were divided at the median. The hazard ratio (HR) and its 95% CI are shown together with the two-tailed log-rank P value. (C) Model for the regulation of ER-α expression and activity by calcineurin. Calcineurin dephosphorylates ER-α at Ser²⁹⁴, which inhibits ER-α degradation mediated by E6AP. Calcineurin also contributes to ER-α activation by estrogen through mTOR activation. Ub, ubiquitination: P, phosphorylation.