TUFT1 is expressed in breast cancer and involved in cancer cell proliferation and survival.

TUFT1 is expressed in breast cancer and involved in cancer cell proliferation and survival.
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TUFT1 在乳腺癌中表达并参与癌细胞增殖和存活

DOI:
10.18632/oncotarget.20472
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发表时间:
2017-09-26
期刊:
影响因子:
--
通讯作者:
Chen B
Chen B
中科院分区:
其他
文献类型:
--
作者:
Liu W;Zhang L;Jin Z;Zhao M;Li Z;Chen G;Sun L;Chen B

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Tuftelin 1 (TUFT1)广泛表达于不同的胚胎组织和成人组织以及一些肿瘤细胞中,在外胚层珐琅质矿化的初始阶段起着重要作用。然而,由于该基因在肿瘤中的作用尚未被彻底研究,其在乳腺癌发展中的功能仍不清楚。我们通过人体标本研究和细胞系研究证实,乳腺癌标本中TUFT1表达水平升高,且TUFT1表达升高与肿瘤大小、组织学分级、淋巴结转移率及预后不良呈正相关。进一步的体外研究表明,在T-47D和MDA-MB-231乳腺癌细胞中,抑制TUFT1表达可显著影响细胞增殖,诱导细胞凋亡,导致g1期细胞周期阻滞。此外,与对照组相比,体内TUFT1表达的降低抑制了肿瘤的生长。此外,微阵列和通路分析表明,TUFT1抑制导致多个信号通路的显著变化,半定量western blot分析显示,TUFT1表达的降低伴随着MAPK信号通路成分的变化。这些结果表明,TUFT1可能是一种新的乳腺癌标志物和潜在的有效治疗靶点。
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.
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