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Abstract Introduction Microtubule-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. Methods 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 (tamoxifen and fulvestrant) and taxanes. Results mRNA 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. Conclusions 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 increases the sensitivity to taxanes in MAPT- and ER-positive breast cancer cells.
Medicine(all), Estradiol, Reverse Transcriptase Polymerase Chain Reaction, Blotting, Western, Estrogen Antagonists, Down-Regulation, Fluorescent Antibody Technique, Breast Neoplasms, Drug Synergism, tau Proteins, Tamoxifen, Estrogen Receptor Modulators, Receptors, Estrogen, Cell Line, Tumor, Humans, Protein Isoforms, Female, Taxoids, RNA, Messenger, RNA, Small Interfering, Fulvestrant, Research Article
Medicine(all), Estradiol, Reverse Transcriptase Polymerase Chain Reaction, Blotting, Western, Estrogen Antagonists, Down-Regulation, Fluorescent Antibody Technique, Breast Neoplasms, Drug Synergism, tau Proteins, Tamoxifen, Estrogen Receptor Modulators, Receptors, Estrogen, Cell Line, Tumor, Humans, Protein Isoforms, Female, Taxoids, RNA, Messenger, RNA, Small Interfering, Fulvestrant, Research Article
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically). | 64 | |
popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network. | Top 10% | |
influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically). | Top 10% | |
impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network. | Top 10% |