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Nuclear T-STAR Protein Expression Correlates with HER2 Status, Hormone Receptor Negativity and Prolonged Recurrence Free Survival in Primary Breast Cancer and Decreased Cancer Cell Growth In Vitro
KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.ORCID iD: 0000-0001-8993-048X
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2013 (English)In: PLoS ONE, ISSN 1932-6203, Vol. 8, no 7, e70596- p.Article in journal (Refereed) Published
Abstract [en]

T-STAR (testis-signal transduction and activation of RNA) is an RNA binding protein, containing an SH3-binding domain and thus potentially playing a role in integration of cell signaling and RNA metabolism. The specific function of T-STAR is unknown and its implication in cancer is poorly characterized. Expression of T-STAR has been reported in human testis, muscle and brain tissues, and is associated with a growth-inhibitory role in immortalized fibroblasts. The aim of this paper was to investigate the functional role of T-STAR through (i) survival analysis of patients with primary invasive breast cancer and (ii) experimental evaluation of the effect of T-STAR on breast cancer cell growth. T-STAR protein expression was analysed by immunohistochemistry (IHC) in tissue microarrays with tumors from 289 patients with primary invasive breast cancer, and correlations to clinicopathological characteristics, recurrence-free and overall survival (RFS and OS) and established tumor markers such as HER2 and ER status were evaluated. In addition, the function of T-STAR was investigated using siRNA-mediated knock-down and overexpression of the gene in six breast cancer cell lines. Of the tumors analysed, 86% showed nuclear T-STAR expression, which was significantly associated with an improved RFS and strongly associated with positive HER2 status and negative hormone receptor status. Furthermore, experimental data showed that overexpression of T-STAR decreased cellular growth while knock-down increased it, as shown both by thymidine incorporation and metabolic activity. In summary, we demonstrate that T-STAR protein expression correlates with an improved RFS in primary breast cancer. This is supported by functional data, indicating that T-STAR regulation is of importance both for breast cancer biology and clinical outcome but future studies are needed to determine a potential role in patient stratification.

Place, publisher, year, edition, pages
2013. Vol. 8, no 7, e70596- p.
Keyword [en]
epidermal growth factor receptor 2, estrogen receptor, RNA binding protein, testis signal transduction and activation of RNA, tumor marker, unclassified drug
National Category
Biological Sciences Medical and Health Sciences
URN: urn:nbn:se:kth:diva-133550DOI: 10.1371/journal.pone.0070596ISI: 000323369700196ScopusID: 2-s2.0-84880809332OAI: diva2:662435
Swedish Cancer Society, 12/0565

QC 20131107

Available from: 2013-11-07 Created: 2013-11-06 Last updated: 2013-11-07Bibliographically approved

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