The estrogen receptor influences microtubule-associated protein tau (MAPT) expression and the selective estrogen receptor inhibitor fulvestrant downregulates MAPT and increases the sensitivity to taxane in breast cancer cells

Abstract

IntroductionMicrotubule-associated protein tau (MAPT) inhibits the function of taxanes and high expression of MAPT decreases the sensitivity to taxanes. The relationship between estrogen receptor (ER) and MAPT in breast cancer is unclear. In this study, we examined the correlation of MAPT expression with the sensitivity of human breast cancer cells to taxanes, and the relationship between ER and MAPT.MethodsThe correlation between MAPT expression and sensitivity to taxanes was investigated in 12 human breast cancer cell lines. Alterations in cellular sensitivity to taxanes were evaluated after knockdown of MAPT expression. ER expression was knocked down or stimulated in MAPT- and ER-positive cell lines to examine the relationship between ER and MAPT. The cells were also treated with hormone drugs (tamoxifen and fulvestrant) and taxanes.ResultsmRNA expression of MAPT did not correlate with sensitivity to taxanes. However, expression of MAPT protein isoforms of less than 70 kDa was correlated with a low sensitivity to taxanes. Downregulation of MAPT increased cellular sensitivity to taxanes. MAPT protein expression was increased by stimulation with 17-β-estradiol or tamoxifen, but decreased by ER downregulation and by fulvestrant, an ER inhibitor. The combination of fulvestrant with taxanes had a synergistic effect, whereas tamoxifen and taxanes had an antagonistic effect.ConclusionsExpression of MAPT protein isoforms of less than 70 kDa is correlated with a low sensitivity to taxanes in breast cancer cells. ER influences MAPT expression and fulvestrant increases the sensitivity to taxanes in MAPT- and ER-positive breast cancer cells.

Microtubule-associated protein tau is associated with the resistance to docetaxel in prostate cancer cell lines

“…In addition, the abnormal expression of tau protein was previously reported in many cancers, and the role of tau in cancer treatment has also been reported by others, such as gastric carcinoma,13,14 breast cancer,12,15,16 and ovarian cancer 9,17…”

Ixabepilone Administered Weekly or Every Three Weeks in HER2-Negative Metastatic Breast Cancer Patients; A Randomized Non-Comparative Phase II Trial

“…In the present series MAPT mRNA and tau protein expression were strongly associated with each other, while high expression of either was associated with favorable outcome. This is in line with ER and PgR being favorable predictors in the present study, since MAPT expression is influenced by ER [46]. It is also in line with the inverse correlation of high MAPT with high Ki67 and TopoIIa-positivity, which are generally associated with poor prognosis.…”

Multivariate Hypergeometric Similarity Measure

“…For example, recent investigations have examined the role of MAPT [27] and GATA3 [28] in breast cancer; while MAPT appears in the top rankings of all four similarity measures in Table 1, GATA3 appears in the rankings of the other three similarity measures, but not in those of the multivariate hypergeometric similarity measure. Additionally, the benefits of examining a single data set across alternative thresholds can be clearly observed through the notably different gene lists for each measure in Tables 1, 2, and 3.…”