SATB1 在乳腺癌发病机制中的作用。

The role of SATB1 in breast cancer pathogenesis.

机构信息

Department of Medicine, University of Miami Miller School of Medicine, 1550 NW 10th Ave (PAP 403), Miami, FL 33136, USA.

出版信息

J Natl Cancer Inst. 2010 Aug 18;102(16):1284-96. doi: 10.1093/jnci/djq243. Epub 2010 Jul 1.

DOI:10.1093/jnci/djq243

PMID:20595686

Abstract

BACKGROUND

SATB1 has been previously proposed as a key protein that controls the development and progression of breast cancer. We explored the potential of the SATB1 protein as a therapeutic target and prognostic marker for human breast cancer.

METHODS

We used aggressive (MDA-MB-231 and BT549) and nonaggressive (SKBR3 and MCF7) breast cancer cell lines to investigate the potential of SATB1 as a therapeutic target. SATB1 mRNA expression was silenced in aggressive cells by use of short hairpin RNAs against SATB1. SATB1 was overexpressed in nonaggressive cells by use of SATB1 expression vectors. We assessed the effect of modifying SATB1 expression on the transformed phenotype by examining anchorage-independent cell proliferation, acinar morphology on matrigel, and migration by wound healing in cultured cells. We examined tumor formation and metastasis, respectively, by use of orthotopic mammary fat pad and tail vein xenograft mouse models (mice were used in groups of six, and in total, 96 mice were used). SATB1 mRNA expression was compared with outcome for patients with primary breast cancer from six previous microarray studies that included a total of 1170 patients. All statistical tests were two-sided.

RESULTS

The transformed phenotype was not suppressed by SATB1 silencing in aggressive cells and was not enhanced by ectopic expression of SATB1 in nonaggressive cells. Modifying SATB1 expression did not alter anchorage-independent cell proliferation, invasive acinar morphology, or cell migration in cultured cells and did not affect tumor formation or metastasis in xenograft mouse models. In addition, SATB1 expression was not associated with decreased overall survival of patients with primary breast cancer in six previous independent microarray studies (overall odds ratio = 0.80, 95% confidence interval = 0.62 to 1.03, P = .10).

CONCLUSION

In contrast to previous studies, we found that SATB1 expression did not promote breast cancer progression and was not associated with breast cancer outcome.

摘要

背景

SATB1 先前被提出是控制乳腺癌发生和发展的关键蛋白。我们探索 SATB1 蛋白作为人类乳腺癌治疗靶点和预后标志物的潜力。

方法

我们使用侵袭性（MDA-MB-231 和 BT549）和非侵袭性（SKBR3 和 MCF7）乳腺癌细胞系，以研究 SATB1 作为治疗靶点的潜力。采用针对 SATB1 的短发夹 RNA 使侵袭性细胞中的 SATB1mRNA 表达沉默。采用 SATB1 表达载体使非侵袭性细胞中的 SATB1 过表达。我们通过检测细胞培养中锚定非依赖性细胞增殖、基质胶中成腔形态和伤口愈合中的迁移，来评估修饰 SATB1 表达对转化表型的影响。我们分别通过使用原位乳腺脂肪垫和尾静脉异种移植小鼠模型来检测肿瘤形成和转移（每组使用 6 只小鼠，共使用 96 只小鼠）。我们比较了来自 6 个先前微阵列研究中 1170 例原发性乳腺癌患者的 SATB1mRNA 表达与患者结局。所有统计学检验均为双侧检验。

结果

SATB1 沉默在侵袭性细胞中未抑制转化表型，而 SATB1 在外源性表达在非侵袭性细胞中也未增强转化表型。在细胞培养中修饰 SATB1 表达并未改变锚定非依赖性细胞增殖、侵袭性腔状形态或细胞迁移，也未影响异种移植小鼠模型中的肿瘤形成或转移。此外，SATB1 表达与 6 个先前独立微阵列研究中原发性乳腺癌患者的总生存时间无相关性（总比值比=0.80，95%置信区间=0.62 至 1.03，P=0.10）。