Abstract

Tuftelin 1 (TUFT1), which plays an important role in the initial stages of the mineralization of ectodermal enamel, is widely expressed in different embryonic and adult tissues and some tumor cells. However, since the roles of this gene have not been thoroughly investigated in tumors, its function in the development of breast cancer remains unclear. We proved both human specimens studies and cell line studies, that TUFT1 expression levels are increased in breast cancer samples, and the increased expression of TUFT1 was shown to be positively correlated with tumor size, histological grade, lymph node metastasis rate, and poor prognosis. Further in vitro studies showed that the inhibition of TUFT1 expression in T-47D and MDA-MB-231 breast cancer cells significantly affected cell proliferation, induced apoptosis, and led to G1-phase cell cycle arrest. Moreover, reduced TUFT1 expression restrained tumor growth compared with the control group in vivo. Furthermore, microarray and pathway analysis demonstrated that TUFT1 inhibition led to significant changes of several signaling pathways and semi-quantitative western blot analysis showed that a decrease in TUFT1 expression was accompanied by changes in MAPK signaling pathway components. The obtained results suggest that TUFT1 may represent a novel breast cancer marker and a potentially effective therapeutic target.

Highlights

  • Breast cancer is one of the most common cancers and it represents the main cause of cancer-related death in women [1]

  • We proved both human specimens studies and cell line studies, that TUFT1 expression levels are increased in breast cancer samples, and the increased expression of TUFT1 was shown to be positively correlated with tumor size, histological grade, lymph node metastasis rate, and poor prognosis

  • TUFT1 expression is increased in breast cancer tissue samples and it correlates with poor prognosis

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Summary

Introduction

Breast cancer is one of the most common cancers and it represents the main cause of cancer-related death in women [1]. Signal transduction pathways can be affected by these molecules, which can further lead to the changes in gene expressions, resulting in abnormal cell proliferation, differentiation, and growth. In order to elucidate molecular mechanisms underlying the development of breast cancer, it is very important to identify a potent and effective diagnostic marker. The understanding of these molecular mechanisms is expected to lead to an improved treatment of breast cancer

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