Tight correlation between expression of the Forkhead transcription factor FOXM1 and HER2 in human breast cancer.
Tight correlation between expression of the Forkhead transcription factor FOXM1 and HER2 in human breast cancer.
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DOI：
10.1186/1471-2407-8-42
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发表时间：
2008-02-06
期刊：
影响因子：
3.8
通讯作者：
Dahl, Edgar
中科院分区：
文献类型：
--
作者：
Bektas, Nuran;ten Haaf, Anette;Veeck, Juergen;Wild, Peter Johannes;Luescher-Firzlaff, Juliane;Hartmann, Arndt;Knuechel, Ruth;Dahl, Edgar
FOXM1调节细胞周期相关基因的表达，这些基因对DNA复制和有丝分裂至关重要。与其在增殖中的作用一致，FOXM1在多种人类肿瘤实体中表达升高。FOXM1是一个令人感兴趣的基因，因为最近FOXM1的化学抑制剂被描述为在体外限制癌细胞的增殖和诱导细胞凋亡，这表明FOXM1抑制剂可能代表有用的抗癌治疗方法。采用免疫组化（IHC）技术，在组织芯片上系统分析了FOXM1在人类浸润性乳腺癌（n = 204）和正常乳腺组织（n = 46）中的表达。此外，采用半定量实时荧光定量PCR技术，对石蜡包埋正常（n = 12）和癌（n = 25）乳腺组织标本，以及良性（n = 3）和恶性乳腺细胞系（n = 8）进行FOXM1表达检测。采用SPSS 14.0版本进行统计分析。研究发现，与正常乳腺组织相比，FOXM1在乳腺癌组织中的RNA和蛋白质水平都过表达（例如，通过实时PCR测量的8.7倍）。我们发现FOXM1表达与HER2免疫组化检测的HER2状态有显著相关性（P < 0.05）。单因素生存分析显示FOXM1蛋白表达与不良预后呈正相关（P = 0.110）。FOXM1可能代表了一种具有预后意义的新型乳腺肿瘤标志物，可以被纳入乳腺癌的多标志物小组。有趣的是，我们发现FOXM1表达与HER2状态呈正相关，这表明FOXM1作为HER2耐药乳腺肿瘤的新药物靶点的潜在作用，因为FOXM1抑制剂用于癌症治疗最近被描述。进一步的研究正在分析FOXM1和HER2之间潜在的相互作用，特别是FOXM1是否直接激活HER2启动子。
FOXM1 regulates expression of cell cycle related genes that are essential for progression into DNA replication and mitosis. Consistent with its role in proliferation, elevated expression of FOXM1 has been reported in a variety of human tumour entities. FOXM1 is a gene of interest because recently chemical inhibitors of FOXM1 were described to limit proliferation and induce apoptosis in cancer cells in vitro, indicating that FOXM1 inhibitors could represent useful anticancer therapeutics. Using immunohistochemistry (IHC) we systematically analysed FOXM1 expression in human invasive breast carcinomas (n = 204) and normal breast tissues (n = 46) on a tissue microarray. Additionally, using semiquantitative realtime PCR, a collection of paraffin embedded normal (n = 12) and cancerous (n = 25) breast tissue specimens as well as benign (n = 3) and malignant mammary cell lines (n = 8) were investigated for FOXM1 expression. SPSS version 14.0 was used for statistical analysis. FOXM1 was found to be overexpressed in breast cancer in comparison to normal breast tissue both on the RNA and protein level (e.g. 8.7 fold as measured by realtime PCR). We found a significant correlation between FOXM1 expression and the HER2 status determined by HER2 immunohistochemistry (P < 0.05). Univariate survival analysis showed a tendency between FOXM1 protein expression and unfavourable prognosis (P = 0.110). FOXM1 may represent a novel breast tumour marker with prognostic significance that could be included into multi-marker panels for breast cancer. Interestingly, we found a positive correlation between FOXM1 expression and HER2 status, pointing to a potential role of FOXM1 as a new drug target in HER2 resistant breast tumour, as FOXM1 inhibitors for cancer treatment were described recently. Further studies are underway to analyse the potential interaction between FOXM1 and HER2, especially whether FOXM1 directly activates the HER2 promoter.
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影响因子：
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作者：
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通讯作者：
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