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      Overexpression of Class III β-tubulin, Sox2, and nuclear Survivin is predictive of taxane resistance in patients with stage III ovarian epithelial cancer

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          Abstract

          Background

          Class III β-tubulin, Sox2, and Survivin play important roles in tumor survival and proliferation. However, the association of these three factors with clinicopathological characteristics, chemoresistance, and survival in patients with ovarian cancer remains controversial.

          Methods

          We investigated the predictive value and correlation among the expression levels of Class III β-tubulin, Sox2, and Survivin in 110 patients with stage III ovarian epithelial cancer, including 58 patients who received taxane-based chemotherapy and 52 patients who received non-taxane-based chemotherapy. Expression of these three factors was immunohistochemically examined in 110 ovarian tumor tissues obtained from patients before chemotherapy.

          Results

          The positive expression rates for Class III β-tubulin, Sox2, and Survivin in ovarian tumor tissues were 59.09 %, 61.82 % and 52.73 %, respectively. The expression of nuclear Survivin and Class III β-tubulin was consistent with that of Sox2 ( p = 0.005 and 0.020, respectively). Positive expression of Class III β-tubulin, Sox2, and nuclear Survivin was significantly associated with chemoresistance to taxane-based chemotherapy ( p = 0.006, 0.007, and 0.009, respectively), but not to non-taxane-based chemotherapy. Additionally, overexpression of Class III β-tubulin, Sox2, and nuclear Survivin predicted poor progression-free survival in patients receiving taxane-based chemotherapy ( p = 0.032, 0.005, and 0.004, respectively).

          Conclusions

          These findings suggest that overexpression of Class III β-tubulin, Sox2, and nuclear Survivin might be predictive of taxane resistance and poor progression-free survival in patients with stage III ovarian epithelial cancer. Expression of these three factors may show positive correlations in these patients.

          Electronic supplementary material

          The online version of this article (doi:10.1186/s12885-015-1553-x) contains supplementary material, which is available to authorized users.

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          Most cited references 40

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          IAP family proteins--suppressors of apoptosis.

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            A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma.

            Inhibitors of programmed cell death (apoptosis) aberrantly prolonging cell viability may contribute to cancer by facilitating the insurgence of mutations and by promoting resistance to therapy. Despite the identification of several new apoptosis inhibitors related to bcl-2 or to the baculovirus IAP gene, it is not clear whether apoptosis inhibition plays a general role in neoplasia. Here, we describe a new human gene encoding a structurally unique IAP apoptosis inhibitor, designated survivin. Survivin contains a single baculovirus IAP repeat and lacks a carboxyl-terminal RING finger. Present during fetal development, survivin is undetectable in terminally differentiated adult tissues. However, survivin becomes prominently expressed in transformed cell lines and in all the most common human cancers of lung, colon, pancreas, prostate and breast, in vivo. Survivin is also found in approximately 50% of high-grade non-Hodgkin's lymphomas (centroblastic, immunoblastic), but not in low-grade lymphomas (lymphocytic). Recombinant expression of survivin counteracts apoptosis of B lymphocyte precursors deprived of interleukin 3 (IL-3). These findings suggest that apoptosis inhibition may be a general feature of neoplasia and identify survivin as a potential new target for apoptosis-based therapy in cancer and lymphoma.
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              Tubulin-targeting chemotherapy impairs androgen receptor activity in prostate cancer.

              Recent insights into the regulation of the androgen receptor (AR) activity led to novel therapeutic targeting of AR function in prostate cancer patients. Docetaxel is an approved chemotherapy for treatment of castration-resistant prostate cancer; however, the mechanism underlying the action of this tubulin-targeting drug is not fully understood. This study investigates the contribution of microtubules and the cytoskeleton to androgen-mediated signaling and the consequences of their inhibition on AR activity in human prostate cancer. Tissue microarrays from docetaxel-treated and untreated prostate cancer patients were comparatively analyzed for prostate-specific antigen (PSA) and AR immunoreactivity. The AR transcriptional activity was determined in prostate cancer cells in vitro, based on PSA mRNA expression and the androgen response element reporter activity. The interaction of AR with tubulin was examined by immunoprecipitation and immunofluorescence. Treatment of prostate cancer patients with docetaxel led to a significant translocation of AR. In untreated specimens, 50% prostate tumor cells exhibited nuclear accumulation of AR, compared with docetaxel-treated tumors that had significantly depleted nuclear AR (38%), paralleled by an increase in cytosolic AR. AR nuclear localization correlated with PSA expression. In vitro, exposure of prostate cancer cells to paclitaxel (1 μmol/L) or nocodazole (5 μg/mL) inhibited androgen-dependent AR nuclear translocation by targeting AR association with tubulin. Introduction of a truncated AR indicated the requirement of the NH(2)-terminal domain for AR-tubulin interaction. Our findings show that in addition to blocking cell division, docetaxel impairs AR signaling, evidence that enables new insights into the therapeutic efficacy of microtubule-targeting drugs in prostate cancer. ©2010 AACR.
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                Author and article information

                Contributors
                jintongdu@sina.cn
                beili008@hotmail.com
                fyl1599@126.com
                y.g.liu@163.com
                530623106@qq.com
                lijisheng@gmail.com
                wenzhou25@sdu.edu.cn
                86-13791122979 , xiuwenwang12@sdu.edu.cn
                Journal
                BMC Cancer
                BMC Cancer
                BMC Cancer
                BioMed Central (London )
                1471-2407
                23 July 2015
                23 July 2015
                2015
                : 15
                Affiliations
                [ ]Department of Chemotherapy, Qilu Hospital of Shandong University, No. 107 Wenhuaxi road, Ji’nan, Shandong 250012 China
                [ ]Shandong Cancer Hospital, Shandong Academy of Medical Science, Ji’nan, Shandong 250012 China
                Article
                1553
                10.1186/s12885-015-1553-x
                4511538
                © Du et al. 2015

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                Categories
                Research Article
                Custom metadata
                © The Author(s) 2015

                Oncology & Radiotherapy

                ovarian cancer, class iii β-tubulin, sox2, survivin, taxane, resistance, survival

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