转化生长因子β受体3（TGFBR3）缺失及其在前列腺癌中的后果

TGFBR3 loss and consequences in prostate cancer.

作者信息

Sharifi Nima, Hurt Elaine M, Kawasaki Brian T, Farrar William L

机构信息

Cancer Stem Cell Section, Laboratory of Cancer Prevention, National Cancer Institute at Frederick, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, Maryland 21702, USA.

出版信息

Prostate. 2007 Feb 15;67(3):301-11. doi: 10.1002/pros.20526.

DOI:10.1002/pros.20526

PMID:17192875

Abstract

BACKGROUND

Resistance to transforming growth factor-beta (TGF-beta) is important in tumorigenesis. TGF-beta resistance mechanisms in prostate cancer are not well understood.

METHODS

We have conducted a systematic analysis of TGF-beta pathway components with a meta-analysis of seven microarray studies using Oncomine and evaluated the results of TGFBR3 expression in prostate cell lines. Furthermore, we knocked down TGFBR3 in prostate epithelial cells and analyzed the consequences of TGFBR3 knockdown.

RESULTS

We found that TGFBR3 is the TGF-beta component most commonly downregulated among localized human prostate cancer studies. TGFBR3 knockdown led to focus formation and enhanced expression of CD133, a marker found on prostate cancer stem cells. DNA microarray analysis of TGFBR3 knockdown cells identified 101 genes regulated by TGFBR3. Seven of these genes show a corresponding decrease in clinical prostate cancer specimens, which include genes involved in prostate mass and vasculature.

CONCLUSIONS

TGFBR3 downregulation is an important step in prostate tumorigenesis.

摘要

背景

对转化生长因子-β（TGF-β）的抗性在肿瘤发生过程中很重要。前列腺癌中TGF-β的抗性机制尚未完全了解。

方法

我们使用Oncomine对七项微阵列研究进行了荟萃分析，对TGF-β信号通路成分进行了系统分析，并评估了TGFBR3在前列腺癌细胞系中的表达结果。此外，我们在前列腺上皮细胞中敲低了TGFBR3，并分析了TGFBR3敲低的后果。

结果

我们发现，在局限性人类前列腺癌研究中，TGFBR3是最常下调的TGF-β成分。TGFBR3敲低导致集落形成，并增强了前列腺癌干细胞标志物CD133的表达。对TGFBR3敲低细胞的DNA微阵列分析确定了101个受TGFBR3调控的基因。其中七个基因在临床前列腺癌标本中相应减少，这些基因包括参与前列腺肿块和脉管系统的基因。