Paired-like Homeodomain Transcription factor 2 expression by breast cancer bone marrow disseminated tumor cells is associated with early recurrent disease development.
Paired-like Homeodomain Transcription factor 2 expression by breast cancer bone marrow disseminated tumor cells is associated with early recurrent disease development.
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DOI：
10.1007/s10549-015-3576-z
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发表时间：
2015-10
影响因子：
3.8
通讯作者：
Aft R
中科院分区：
文献类型：
--
作者：
Pillai SG;Dasgupta N;Siddappa CM;Watson MA;Fleming T;Trinkaus K;Aft R
乳腺癌患者骨髓中播散性肿瘤细胞(DTC)的存在是早期复发的预后指标。在本研究中，我们分析了乳腺癌患者BM细胞的基因表达谱，以确定与DTC相关的分子特征及其与转移结果的相关性。我们通过基因表达谱分析了30例II/III期乳腺癌患者的骨髓，并分析了其表达与转移疾病发展的相关性。对候选基因PITX2在乳腺癌细胞系中的表达和表型进行了分析。在MDAMB231细胞系中敲除PITX2，进行基因表达分析和细胞侵袭力检测。逆转录-聚合酶链式反应证实了多种信号通路分子的表达。我们发现，在正常健康志愿者的骨髓中不存在成对的同源盒转录因子-2(PITX2)的表达，当在乳腺癌患者的骨髓中检测到PITX2时，与早期转移疾病的发展显著相关(p=0.0062)。抑制PITX2的表达可显著降低MDAMB231细胞的侵袭力。有三个基因--NKD1、LEF1和DKK4--在PITX2抑制后显著下调。PITX2在早期乳腺癌患者骨髓中的表达与早期复发的风险相关。此外，PITX2可能通过影响Wnt/β-catenin信号通路相关基因的表达而在肿瘤转移过程中发挥作用。本文的在线版本(doi：10.1007/s10549-0153576-z)包含补充材料，授权用户可以使用。
The presence of disseminated tumor cells (DTCs) in the bone marrow (BM) of breast cancer patients is prognostic for early relapse. In the present study, we analyzed the gene expression profiles from BM cells of breast cancer patients to identify molecular signatures associated with DTCs and their relevance to metastatic outcome. We analyzed BM from 30 patients with stage II/III breast cancer by gene expression profiling and correlated expression with metastatic disease development. A candidate gene, PITX2, was analyzed for expression and phenotype in breast cancer cell lines. PITX2 was knocked down in the MDAMB231 cell lines for gene expression analysis and cell invasiveness. Expression of various signaling pathway molecules was confirmed by RT–PCR. We found that the expression of Paired-like Homeobox Transcription factor-2 (PITX2) is absent in the BM of normal healthy volunteers and, when detected in the BM of breast cancer patients, is significantly correlated with early metastatic disease development (p = 0.0062). Suppression of PITX2 expression significantly reduced invasiveness in MDAMB231 cells. Three genes—NKD1, LEF1, and DKK4—were significantly downregulated in response to PITX2 suppression. Expression of PITX2 in BM of early-stage breast cancer patients is associated with risk for early disease recurrence. Furthermore, PITX2 likely plays a role in the metastatic process through its effect on the expression of genes associated with the Wnt/beta-Catenin signaling pathway. The online version of this article (doi:10.1007/s10549-015-3576-z) contains supplementary material, which is available to authorized users.