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NFIB 是雌激素受体阴性乳腺癌的潜在靶点。

NFIB is a potential target for estrogen receptor-negative breast cancers.

机构信息

Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Republic of Korea.

出版信息

Mol Oncol. 2011 Dec;5(6):538-44. doi: 10.1016/j.molonc.2011.08.002. Epub 2011 Aug 8.

DOI:10.1016/j.molonc.2011.08.002
PMID:21925980
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5528324/
Abstract

BACKGROUND

The association between nuclear factor I/B (NFIB) gene and triple negative breast cancer has been previously suggested.

METHODS

We investigated the relationship between NFIB mRNA and protein expression and molecular subtypes of breast cancer as well as the effect of NFIB silencing on the proliferation and apoptosis of breast cancer cells. Also, the clinical importance of NFIB expression was investigated in 163 breast cancer patients.

RESULTS

By using 20 frozen human breast cancer tissues and various breast cancer cell lines, we observed a significant high level of NFIB mRNA level in triple negative breast cancer. NFIB protein was upregulated in ER negative breast cancer tissues but the expression level was similar between HER2 subtype and triple negative subtype. The clinical significance of NFIB was further examined in a tissue microarray from 163 invasive breast cancer patients, and the immunohistochemistry results showed a significant association between NFIB expression and nuclear grade, ER, and HER2 expression status. NFIB positive tumors were more likely to have high nuclear grade, ER negativity and HER2 over-expression. HCC1954 cells transfected with siRNA against NFIB showed a significant reduction in cell proliferation and increase in apoptotic signaling pathway.

CONCLUSIONS

Our results show a potential role of NFIB as a novel target in ER negative breast cancers.

摘要

背景

核因子 I/B(NFIB)基因与三阴性乳腺癌之间的关联先前已被提出。

方法

我们研究了 NFIB mRNA 和蛋白表达与乳腺癌分子亚型之间的关系,以及 NFIB 沉默对乳腺癌细胞增殖和凋亡的影响。此外,我们还在 163 名乳腺癌患者中研究了 NFIB 表达的临床重要性。

结果

通过使用 20 份冷冻人乳腺癌组织和各种乳腺癌细胞系,我们观察到三阴性乳腺癌中 NFIB mRNA 水平显著升高。NFIB 蛋白在 ER 阴性乳腺癌组织中上调,但在 HER2 亚型和三阴性亚型之间表达水平相似。我们在 163 例浸润性乳腺癌患者的组织微阵列中进一步研究了 NFIB 的临床意义,免疫组化结果表明 NFIB 表达与核分级、ER 和 HER2 表达状态之间存在显著关联。NFIB 阳性肿瘤更有可能具有高核分级、ER 阴性和 HER2 过表达。用针对 NFIB 的 siRNA 转染 HCC1954 细胞后,细胞增殖显著减少,凋亡信号通路增加。

结论

我们的结果表明 NFIB 作为 ER 阴性乳腺癌的一个新的潜在靶点。

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本文引用的文献

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Expression of microRNA and their gene targets are dysregulated in preinvasive breast cancer.在乳腺癌前病变中,miRNA 的表达及其基因靶标失调。
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Comprehensive analysis of the MYB-NFIB gene fusion in salivary adenoid cystic carcinoma: Incidence, variability, and clinicopathologic significance.全面分析唾液腺腺样囊性癌中的 MYB-NFIB 基因融合:发生率、变异性及临床病理意义。
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Recurrent fusion of MYB and NFIB transcription factor genes in carcinomas of the breast and head and neck.MYB和NFIB转录因子基因在乳腺癌和头颈癌中反复融合。
Proc Natl Acad Sci U S A. 2009 Nov 3;106(44):18740-4. doi: 10.1073/pnas.0909114106. Epub 2009 Oct 19.
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HMGA2-NFIB fusion in a pediatric intramuscular lipoma: a novel case of NFIB alteration in a large deep-seated adipocytic tumor.小儿肌内脂肪瘤中的HMGA2-NFIB融合:一种大型深部脂肪细胞肿瘤中NFIB改变的新病例
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miR-21 as a key regulator of oncogenic processes.微小RNA-21作为致癌过程的关键调节因子。
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NFIB rearrangement in superficial, retroperitoneal, and colonic lipomas with aberrations involving chromosome band 9p22.浅表、腹膜后及结肠脂肪瘤中涉及9p22染色体带畸变的NFIB重排。
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miR-21 Gene expression triggered by AP-1 is sustained through a double-negative feedback mechanism.由AP-1触发的miR-21基因表达通过双负反馈机制得以维持。
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