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Wnt-β-catenin-Tcf-4 信号转导调控的侵袭能力依赖于乳腺癌中骨桥蛋白的表达。

Wnt-β-catenin-Tcf-4 signalling-modulated invasiveness is dependent on osteopontin expression in breast cancer.

机构信息

Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast BT9 7BL, UK.

出版信息

Br J Cancer. 2011 Aug 9;105(4):542-51. doi: 10.1038/bjc.2011.269. Epub 2011 Jul 19.

DOI:10.1038/bjc.2011.269
PMID:21772333
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3170969/
Abstract

BACKGROUND

We have previously demonstrated that Tcf-4 regulates osteopontin (OPN) in rat breast epithelial cells, Rama37. In this report, we have examined the importance of this regulation in human breast cancer.

METHODS

The regulatory roles of Tcf-4 on cell invasion and OPN expression were investigated. The mRNA expression of Tcf-4 and OPN, and survival of breast cancer patients were correlated.

RESULTS

Tcf-4 enhanced cell invasion in both MCF10AT and MDA MB 231 breast cancer cells by transcriptionally activating OPN expression. Osteopontin was activated by Wnt signalling in MDA MB 231 cells. Paradoxical results on Tcf-4-regulated OPN expression in MCF10AT (activation) and Rama37 (repression) cells were shown to be a result of differential Wnt signalling competency in MCF10AT and Rama37 cells. High levels of OPN and Tcf-4 mRNA expression were significantly associated with survival in breast cancer patients. Most importantly, Tcf-4-positive patients had a poorer prognosis when OPN was overexpressed, while OPN-negative patients had a better prognosis when Tcf-4 was overexpressed.

CONCLUSION

Our results suggest that Tcf-4 can act as a repressor or activator of breast cancer progression by regulating OPN expression in a Wnt-dependent manner and that Tcf-4 and OPN together may be a novel prognostic indicator for breast cancer progression.

摘要

背景

我们之前已经证明 Tcf-4 在大鼠乳腺上皮细胞 Rama37 中调节骨桥蛋白（OPN）。在本报告中，我们研究了这种调节在人乳腺癌中的重要性。

方法

研究了 Tcf-4 对细胞侵袭和 OPN 表达的调节作用。分析了 Tcf-4 和 OPN 的 mRNA 表达与乳腺癌患者生存的相关性。

结果

Tcf-4 通过转录激活 OPN 表达增强了 MCF10AT 和 MDA MB 231 乳腺癌细胞的侵袭能力。骨桥蛋白在 MDA MB 231 细胞中通过 Wnt 信号被激活。在 MCF10AT（激活）和 Rama37（抑制）细胞中，Tcf-4 调节 OPN 表达的结果呈现出相反的情况，这是由于 MCF10AT 和 Rama37 细胞中 Wnt 信号的能力不同。高水平的 OPN 和 Tcf-4 mRNA 表达与乳腺癌患者的生存显著相关。最重要的是，当 OPN 过表达时，Tcf-4 阳性患者的预后较差，而当 Tcf-4 过表达时，OPN 阴性患者的预后较好。

结论

我们的研究结果表明，Tcf-4 可以通过调节 OPN 的表达，以依赖 Wnt 的方式作为乳腺癌进展的抑制剂或激活剂，并且 Tcf-4 和 OPN 可能共同成为乳腺癌进展的新型预后指标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e755/3170969/01951f447583/bjc2011269f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e755/3170969/e098fd242c2b/bjc2011269f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e755/3170969/d901c501b807/bjc2011269f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e755/3170969/585d40249eac/bjc2011269f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e755/3170969/55436c94fc8b/bjc2011269f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e755/3170969/01351fc535dd/bjc2011269f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e755/3170969/01951f447583/bjc2011269f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e755/3170969/e098fd242c2b/bjc2011269f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e755/3170969/d901c501b807/bjc2011269f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e755/3170969/585d40249eac/bjc2011269f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e755/3170969/55436c94fc8b/bjc2011269f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e755/3170969/01351fc535dd/bjc2011269f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e755/3170969/01951f447583/bjc2011269f6.jpg

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