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Open Access 01-06-2010 | Research article

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

Authors: Hirokuni Ikeda, Naruto Taira, Fumikata Hara, Takeo Fujita, Hiromasa Yamamoto, Junichi Soh, Shinichi Toyooka, Tomohiro Nogami, Tadahiko Shien, Hiroyoshi Doihara, Shinichiro Miyoshi

Published in: Breast Cancer Research | Issue 3/2010

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.

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Title: 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
Authors: Hirokuni Ikeda
Naruto Taira
Fumikata Hara
Takeo Fujita
Hiromasa Yamamoto
Junichi Soh
Shinichi Toyooka
Tomohiro Nogami
Tadahiko Shien
Hiroyoshi Doihara
Shinichiro Miyoshi
Publication date: 01-06-2010
Publisher: BioMed Central
Published in: Breast Cancer Research / Issue 3/2010
Electronic ISSN: 1465-542X
DOI: https://doi.org/10.1186/bcr2598

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Abstract

Introduction

Methods

Results

Conclusions

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