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
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
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DOI：
10.1186/bcr2598
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发表时间：
2010-01-01
影响因子：
7.4
通讯作者：
Miyoshi, Shinichiro
中科院分区：
文献类型：
--
作者：
Ikeda, Hirokuni;Taira, Naruto;Miyoshi, Shinichiro
简介：微管相关蛋白tau（MAPT）抑制紫杉烷类药物的功能，MAPT的高表达降低了紫杉烷类药物的敏感性。乳腺癌中雌激素受体（ER）与MAPT的关系尚不清楚。在这项研究中，我们研究了MAPT表达与人乳腺癌细胞对紫杉烷类药物的敏感性的相关性，以及ER和MAPT之间的关系。方法：MAPT表达与紫杉烷类药物敏感性之间的相关性在12个人乳腺癌细胞系进行了研究。在MAPT表达敲低后评价细胞对紫杉烷类敏感性的改变。在MAPT和ER阳性细胞系中敲低或刺激ER表达，以检查ER和MAPT之间的关系。结果：MAPT mRNA表达与细胞对紫杉烷类药物的敏感性无关。然而，表达MAPT蛋白亚型小于70 kDa的紫杉烷类药物的敏感性低。MAPT的下调增加了细胞对紫杉烷的敏感性。MAPT蛋白表达增加刺激与17-β-雌二醇或他莫昔芬，但减少ER下调和氟维司群，ER抑制剂。氟维司群与紫杉烷类药物的组合具有协同作用，而他莫昔芬和紫杉烷类药物具有拮抗作用。结论：MAPT蛋白亚型的表达小于70 kDa的乳腺癌细胞中紫杉烷类药物的敏感性低。ER影响MAPT表达，氟维司群增加MAPT和ER阳性乳腺癌细胞对紫杉烷的敏感性。
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-beta-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.