Antiproliferative effects of TUBB3 in ERα-positive postmenopausal breast cancer model cells.

Long-term estrogen-deprived (LTED) cells were obtained from parental MCF-7 breast cancer (BC) cells cultured under conditions of prolonged estrogen deprivation. In LTED cells, which mimic estrogen receptor α (ERα)-positive BC that has relapsed after endocrine therapy, βIII-tubulin (TUBB3) expression is downregulated. However, the biological significance of TUBB3 downregulation is unclear. To address this, we assessed the effects of siRNAs targeting individual TUBB isotypes. Among of them, only TUBB3-targeting siRNA stimulated the proliferation of MCF-7 cells, but it did not affect LTED cells. After treating LTED cells with 17β-estradiol (E2), the upregulation of TUBB3 expression and antiproliferative effects were detected, suggesting that TUBB3 mediates the antiproliferative effects of E2. Furthermore, the attenuated TUBB3 expression was related to poor prognosis in patients with ERα-positive BC receiving endocrine therapy. These findings identify TUBB3 as an E2-sensitive antiproliferative molecule in ERα-positive BC cells, suggesting that it could be targeted for endocrine therapy-resistant BC.