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Int. J. Mol. Sci. 2015, 16(2), 3419-3433; doi:10.3390/ijms16023419

Three-Dimensional Collagen Type I Matrix Up-Regulates Nuclear Isoforms of the Microtubule Associated Protein Tau Implicated in Resistance to Paclitaxel Therapy in Ovarian Carcinoma

1
Department of Biopharmaceutical Sciences, University of Illinois at Chicago, 833 South Wood Street, Chicago, IL 60612, USA
2
Department of Pathology, University of Illinois at Chicago, 840 South Wood Street, Chicago, IL 60612, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Anthony Lemarié
Received: 25 November 2014 / Revised: 22 January 2015 / Accepted: 27 January 2015 / Published: 4 February 2015
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
View Full-Text   |   Download PDF [5059 KB, uploaded 4 February 2015]   |  

Abstract

Epithelial ovarian carcinoma is the deadliest gynecologic malignancy. One reason underlying treatment failure is resistance to paclitaxel. Expression of the microtubule associated protein tau has recently been proposed as a predictor of response to paclitaxel in ovarian carcinoma patients. Expression of tau was probed using immunohistochemistry in 312 specimens of primary, and 40 specimens of metastatic, ovarian carcinoma. Serous epithelial ovarian carcinoma cell line models were used to determine the expression of tau by Western blot and immunofluorescence staining. Subcellular fractionation and Western blot were employed to examine nuclear and cytoplasmic localization of tau. Gene silencing and clonogenic assays were used to evaluate paclitaxel response. Tau was expressed in 44% of all tested cases. Among the primary serous epithelial ovarian carcinoma cases, 46% were tau-positive. Among the metastatic serous epithelial ovarian carcinomas, 63% were tau-positive. Cell culture experiments demonstrated that tau was expressed in multiple isoforms. Three-dimensional collagen I matrix culture conditions resulted in up-regulation of tau protein. Silencing of tau with specific siRNAs in a combination with three-dimensional culture conditions led to a significant decrease of the clonogenic ability of cells treated with paclitaxel. The data suggest that reduction of tau expression may sensitize ovarian carcinoma to the paclitaxel treatment. View Full-Text
Keywords: serous epithelial ovarian carcinoma; microtubule associated protein tau; paclitaxel; three-dimensional collagen matrix serous epithelial ovarian carcinoma; microtubule associated protein tau; paclitaxel; three-dimensional collagen matrix
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Gurler, H.; Yu, Y.; Choi, J.; Kajdacsy-Balla, A.A.; Barbolina, M.V. Three-Dimensional Collagen Type I Matrix Up-Regulates Nuclear Isoforms of the Microtubule Associated Protein Tau Implicated in Resistance to Paclitaxel Therapy in Ovarian Carcinoma. Int. J. Mol. Sci. 2015, 16, 3419-3433.

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Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
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