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
2013 (English)In: PLoS ONE, ISSN 1932-6203, Vol. 8, no 7, e70596- p.Article in journal (Refereed) Published
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.
epidermal growth factor receptor 2, estrogen receptor, RNA binding protein, testis signal transduction and activation of RNA, tumor marker, unclassified drug
Biological Sciences Medical and Health Sciences
IdentifiersURN: urn:nbn:se:kth:diva-133550DOI: 10.1371/journal.pone.0070596ISI: 000323369700196ScopusID: 2-s2.0-84880809332OAI: oai:DiVA.org:kth-133550DiVA: diva2:662435
FunderSwedish Cancer Society, 12/0565
QC 201311072013-11-072013-11-062013-11-07Bibliographically approved