Microtubule-associated protein tau (MAPT) inhibits the function of taxanes and high expression of MAPT decreased 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.

The 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 (fulvestrant and tamoxifen) and taxanes.

mRNA expression of MAPT did not correlate with protein expression or the 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 decreased by downregulation of ER and by fulvestrant, an ER inhibitor; but increased by stimulation with 17-beta-estradiol or tamoxifen. The combination of fulvestrant with taxanes had a synergistic effect, whereas tamoxifen and taxanes had an antagonistic effect.

Expression 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 increased the sensitivity to taxanes in MAPT- and ER-positive breast cancer cells.

The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production