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首页> 外文期刊>Journal of Cellular Physiology >Characterization of BCAR4, a novel oncogene causing endocrine resistance in human breast cancer cells.
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Characterization of BCAR4, a novel oncogene causing endocrine resistance in human breast cancer cells.

机译：BCAR4特征,小说致癌基因导致人类乳房内分泌阻力癌细胞。

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Resistance to the antiestrogen tamoxifen remains a major problem in the management of estrogen receptor-positive breast cancer. Knowledge on the resistance mechanisms is needed to develop more effective therapies. Breast cancer antiestrogen resistance 4 (BCAR4) was identified in a functional screen for genes involved in tamoxifen resistance. BCAR4 is expressed in 27% of primary breast tumors. In patients treated with tamoxifen for metastized disease high BCAR4 mRNA levels are associated with reduced clinical benefit and progression-free survival. Regarding tumor aggressiveness high BCAR4 mRNA levels are associated with a shorter metastasis free survival and overall survival. In the present study, we investigated the role of BCAR4 in endocrine resistance. Forced expression of BCAR4 in human ZR-75-1 and MCF7 breast cancer cells resulted in cell proliferation in the absence of estrogen and in the presence of various antiestrogens. Inhibition of estrogen receptor 1 (ESR1) expression with small interfering RNA (siRNA), implied that the BCAR4-induced mechanism of resistance is independent of ESR1. Highly conserved BCAR4 homologues of rhesus monkey, green monkey, and the less conserved common marmoset gene induced tamoxifen-resistant cell proliferation, in contrast to the distant BCAR4 homologues of bovine and rabbit. Injection of BCAR4-expressing ZR-75-1 cells into nude mice resulted in rapidly growing tumors. In silico analysis showed that BCAR4 mRNA is highly expressed in human placenta and oocyte, and absent in other normal tissues. In conclusion, BCAR4 is a strong transforming gene causing estrogen-independent growth and antiestrogen resistance, and induces tumor formation in vivo. Due to its restricted expression, BCAR4 may be a good target for treating antiestrogen-resistant breast cancer.
机译：抵抗抗雌激素它莫西芬仍然是一个主要问题在雌激素的管理受体阳性乳腺癌。耐药机制需要开发更多有效的治疗方法。4 (BCAR4)被发现在一个基因功能筛选参与它莫西芬阻力。乳腺肿瘤。metastized疾病BCAR4 mRNA水平高与临床效益和降低有关无进展生存。攻击性BCAR4 mRNA水平高与短转移自由有关生存和总生存期。研究中,我们调查了BCAR4的角色内分泌阻力。在人类zr - 75 - 1和乳腺癌MCF7细胞导致细胞增殖没有雌激素和在不同的存在抗雌激素。小干扰RNA (ESR1)表达式(核),暗示BCAR4-induced机制的阻力ESR1无关。守恒BCAR4同系物的恒河猴,绿猴,守恒的常见的越少绒猴的基因诱导tamoxifen-resistant细胞增殖,与遥远的BCAR4同系物的牛和兔子。BCAR4-expressing zr - 75 - 1细胞裸鼠导致肿瘤迅速增长。分析表明,BCAR4 mRNA高度在人类胎盘和卵母细胞中表达,没有在其他正常组织。BCAR4是强大的转化基因引起estrogen-independent增长和抗雌激素阻力和体内诱发肿瘤的形成。由于其限制表达式,BCAR4可能是一个治疗antiestrogen-resistant好目标乳腺癌。

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