Cargando…

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

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 expressi...

Descripción completa

Detalles Bibliográficos
Autores principales: Ikeda, Hirokuni, Taira, Naruto, Hara, Fumikata, Fujita, Takeo, Yamamoto, Hiromasa, Soh, Junichi, Toyooka, Shinichi, Nogami, Tomohiro, Shien, Tadahiko, Doihara, Hiroyoshi, Miyoshi, Shinichiro
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2917038/
https://www.ncbi.nlm.nih.gov/pubmed/20579400
http://dx.doi.org/10.1186/bcr2598
_version_ 1782185045714272256
author Ikeda, Hirokuni
Taira, Naruto
Hara, Fumikata
Fujita, Takeo
Yamamoto, Hiromasa
Soh, Junichi
Toyooka, Shinichi
Nogami, Tomohiro
Shien, Tadahiko
Doihara, Hiroyoshi
Miyoshi, Shinichiro
author_facet Ikeda, Hirokuni
Taira, Naruto
Hara, Fumikata
Fujita, Takeo
Yamamoto, Hiromasa
Soh, Junichi
Toyooka, Shinichi
Nogami, Tomohiro
Shien, Tadahiko
Doihara, Hiroyoshi
Miyoshi, Shinichiro
author_sort Ikeda, Hirokuni
collection PubMed
description 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.
format Text
id pubmed-2917038
institution National Center for Biotechnology Information
language English
publishDate 2010
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-29170382010-08-06 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 Ikeda, Hirokuni Taira, Naruto Hara, Fumikata Fujita, Takeo Yamamoto, Hiromasa Soh, Junichi Toyooka, Shinichi Nogami, Tomohiro Shien, Tadahiko Doihara, Hiroyoshi Miyoshi, Shinichiro Breast Cancer Res Research Article 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. BioMed Central 2010 2010-06-28 /pmc/articles/PMC2917038/ /pubmed/20579400 http://dx.doi.org/10.1186/bcr2598 Text en Copyright ©2010 Ikeda et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Ikeda, Hirokuni
Taira, Naruto
Hara, Fumikata
Fujita, Takeo
Yamamoto, Hiromasa
Soh, Junichi
Toyooka, Shinichi
Nogami, Tomohiro
Shien, Tadahiko
Doihara, Hiroyoshi
Miyoshi, Shinichiro
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
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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2917038/
https://www.ncbi.nlm.nih.gov/pubmed/20579400
http://dx.doi.org/10.1186/bcr2598
work_keys_str_mv AT ikedahirokuni theestrogenreceptorinfluencesmicrotubuleassociatedproteintaumaptexpressionandtheselectiveestrogenreceptorinhibitorfulvestrantdownregulatesmaptandincreasesthesensitivitytotaxaneinbreastcancercells
AT tairanaruto theestrogenreceptorinfluencesmicrotubuleassociatedproteintaumaptexpressionandtheselectiveestrogenreceptorinhibitorfulvestrantdownregulatesmaptandincreasesthesensitivitytotaxaneinbreastcancercells
AT harafumikata theestrogenreceptorinfluencesmicrotubuleassociatedproteintaumaptexpressionandtheselectiveestrogenreceptorinhibitorfulvestrantdownregulatesmaptandincreasesthesensitivitytotaxaneinbreastcancercells
AT fujitatakeo theestrogenreceptorinfluencesmicrotubuleassociatedproteintaumaptexpressionandtheselectiveestrogenreceptorinhibitorfulvestrantdownregulatesmaptandincreasesthesensitivitytotaxaneinbreastcancercells
AT yamamotohiromasa theestrogenreceptorinfluencesmicrotubuleassociatedproteintaumaptexpressionandtheselectiveestrogenreceptorinhibitorfulvestrantdownregulatesmaptandincreasesthesensitivitytotaxaneinbreastcancercells
AT sohjunichi theestrogenreceptorinfluencesmicrotubuleassociatedproteintaumaptexpressionandtheselectiveestrogenreceptorinhibitorfulvestrantdownregulatesmaptandincreasesthesensitivitytotaxaneinbreastcancercells
AT toyookashinichi theestrogenreceptorinfluencesmicrotubuleassociatedproteintaumaptexpressionandtheselectiveestrogenreceptorinhibitorfulvestrantdownregulatesmaptandincreasesthesensitivitytotaxaneinbreastcancercells
AT nogamitomohiro theestrogenreceptorinfluencesmicrotubuleassociatedproteintaumaptexpressionandtheselectiveestrogenreceptorinhibitorfulvestrantdownregulatesmaptandincreasesthesensitivitytotaxaneinbreastcancercells
AT shientadahiko theestrogenreceptorinfluencesmicrotubuleassociatedproteintaumaptexpressionandtheselectiveestrogenreceptorinhibitorfulvestrantdownregulatesmaptandincreasesthesensitivitytotaxaneinbreastcancercells
AT doiharahiroyoshi theestrogenreceptorinfluencesmicrotubuleassociatedproteintaumaptexpressionandtheselectiveestrogenreceptorinhibitorfulvestrantdownregulatesmaptandincreasesthesensitivitytotaxaneinbreastcancercells
AT miyoshishinichiro theestrogenreceptorinfluencesmicrotubuleassociatedproteintaumaptexpressionandtheselectiveestrogenreceptorinhibitorfulvestrantdownregulatesmaptandincreasesthesensitivitytotaxaneinbreastcancercells
AT ikedahirokuni estrogenreceptorinfluencesmicrotubuleassociatedproteintaumaptexpressionandtheselectiveestrogenreceptorinhibitorfulvestrantdownregulatesmaptandincreasesthesensitivitytotaxaneinbreastcancercells
AT tairanaruto estrogenreceptorinfluencesmicrotubuleassociatedproteintaumaptexpressionandtheselectiveestrogenreceptorinhibitorfulvestrantdownregulatesmaptandincreasesthesensitivitytotaxaneinbreastcancercells
AT harafumikata estrogenreceptorinfluencesmicrotubuleassociatedproteintaumaptexpressionandtheselectiveestrogenreceptorinhibitorfulvestrantdownregulatesmaptandincreasesthesensitivitytotaxaneinbreastcancercells
AT fujitatakeo estrogenreceptorinfluencesmicrotubuleassociatedproteintaumaptexpressionandtheselectiveestrogenreceptorinhibitorfulvestrantdownregulatesmaptandincreasesthesensitivitytotaxaneinbreastcancercells
AT yamamotohiromasa estrogenreceptorinfluencesmicrotubuleassociatedproteintaumaptexpressionandtheselectiveestrogenreceptorinhibitorfulvestrantdownregulatesmaptandincreasesthesensitivitytotaxaneinbreastcancercells
AT sohjunichi estrogenreceptorinfluencesmicrotubuleassociatedproteintaumaptexpressionandtheselectiveestrogenreceptorinhibitorfulvestrantdownregulatesmaptandincreasesthesensitivitytotaxaneinbreastcancercells
AT toyookashinichi estrogenreceptorinfluencesmicrotubuleassociatedproteintaumaptexpressionandtheselectiveestrogenreceptorinhibitorfulvestrantdownregulatesmaptandincreasesthesensitivitytotaxaneinbreastcancercells
AT nogamitomohiro estrogenreceptorinfluencesmicrotubuleassociatedproteintaumaptexpressionandtheselectiveestrogenreceptorinhibitorfulvestrantdownregulatesmaptandincreasesthesensitivitytotaxaneinbreastcancercells
AT shientadahiko estrogenreceptorinfluencesmicrotubuleassociatedproteintaumaptexpressionandtheselectiveestrogenreceptorinhibitorfulvestrantdownregulatesmaptandincreasesthesensitivitytotaxaneinbreastcancercells
AT doiharahiroyoshi estrogenreceptorinfluencesmicrotubuleassociatedproteintaumaptexpressionandtheselectiveestrogenreceptorinhibitorfulvestrantdownregulatesmaptandincreasesthesensitivitytotaxaneinbreastcancercells
AT miyoshishinichiro estrogenreceptorinfluencesmicrotubuleassociatedproteintaumaptexpressionandtheselectiveestrogenreceptorinhibitorfulvestrantdownregulatesmaptandincreasesthesensitivitytotaxaneinbreastcancercells