当前位置： SCI文献检索 > PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA期刊下所有文献 > Microtubule-associated protein tau: a marker of paclitaxel sensitivity in breast cancer.

Microtubule-associated protein tau: a marker of paclitaxel sensitivity in breast cancer.

Abstract：

:Breast cancers show variable sensitivity to paclitaxel. There is no diagnostic test to identify tumors that are sensitive to this drug. We used U133A chips to identify genes that are associated with pathologic complete response (pCR) to preoperative paclitaxel-containing chemotherapy in stage I-III breast cancer (n = 82). Tau was the most differentially expressed gene. Tumors with pCR had significantly lower (P < 0.3 x 10(-5)) mRNA expression. Tissue arrays from 122 independent but similarly treated patients were used for validation by immunohistochemistry. Seventy-four percent of pCR cases were tau protein negative; the odds ratio for pCR was 3.7 (95% confidence interval, 1.6-8.6; P = 0.0013). In multivariate analysis, nuclear grade (P < 0.01), age <50 (P = 0.03), and tau-negative status (P = 0.04) were independent predictors of pCR. Small interfering RNA experiments were performed to examine whether down-regulation of tau increases sensitivity to chemotherapy in vitro. Down-regulation of tau increased sensitivity of breast cancer cells to paclitaxel but not to epirubicin. Tubulin polymerization assay was used to assess whether tau modulates binding of paclitaxel to tubulin. Preincubation of tubulin with tau resulted in decreased paclitaxel binding and reduced paclitaxel-induced microtubule polymerization. These data suggest that low tau expression renders microtubules more vulnerable to paclitaxel and makes breast cancer cells hypersensitive to this drug. Low tau expression may be used as a marker to select patients for paclitaxel therapy. Inhibition of tau function might be exploited as a therapeutic strategy to increase sensitivity to paclitaxel.

journal_name

Proc Natl Acad Sci U S A

journal_title

Proceedings of the National Academy of Sciences of the United States of America

authors

Rouzier R,Rajan R,Wagner P,Hess KR,Gold DL,Stec J,Ayers M,Ross JS,Zhang P,Buchholz TA,Kuerer H,Green M,Arun B,Hortobagyi GN,Symmans WF,Pusztai L

doi

10.1073/pnas.0408974102

keywords:

subject

Has Abstract

pub_date

2005-06-07 00:00:00

pages

8315-20

issue

eissn

0027-8424

issn

1091-6490

pii

0408974102

journal_volume

102

pub_type

杂志文章

在线工具

Microtubule-associated protein tau: a marker of paclitaxel sensitivity in breast cancer.