在恶性子宫内膜中，FGF2转录水平与EGF和IGF-1呈正相关。

FGF2 transcript levels are positively correlated with EGF and IGF-1 in the malignant endometrium.

作者信息

Soufla Giannoula, Sifakis Stavros, Spandidos Demetrios A

机构信息

Department of Virology, Medical School, University of Crete, PO Box 1527, Heraklion 71003, Crete, Greece.

出版信息

Cancer Lett. 2008 Feb 8;259(2):146-55. doi: 10.1016/j.canlet.2007.10.002. Epub 2007 Nov 19.

DOI:10.1016/j.canlet.2007.10.002

PMID:18006148

Abstract

BACKGROUND

Epidermal and insulin-like growth factors (EGF, IGFs) act as mitogens promoting endothelial cell proliferation and differentiation. Accumulating evidence for interactions between EGF and IGF signaling pathways has been reported. Fibroblast growth factor-2 (FGF2) is also mitogenic for various cell types and is associated with regulation of tumor angiogenesis and metastasis. However EGF, IGF-1 and FGF2 transcript levels have been scarcely investigated in endometrial carcinoma.

METHODS

In the present study, we evaluated the mRNA expression pattern of EGF, IGF-1 and FGF2 by using Comparative Quantitative real-time RT-PCR assay in 30 endometrial cancer specimens and an equal number of adjacent normal tissues.

RESULTS

Both overexpression and down-regulation of EGF, IGF-1 and FGF2 was demonstrated in endometrial cancer compared to the adjacent normal specimens; however the main features of cancer were IGF-1 and EGF down-regulation and FGF2 up-regulation. Different co-expression patterns of all three factors were displayed in normal and malignant endometrium. Interestingly, FGF2 mRNA was positively correlated with EGF and IGF-1 transcript levels in endometrial cancer (P=0.024 and P=0.006, respectively), while no co-expression was observed in the adjacent normal specimens. Furthermore, endometrial tissue-pair analysis revealed a significant positive correlation between EGF and IGF-1 (P=0.010), supporting the hypothesis of a cross-talk between IGF- and EGF-mediated signaling pathways in endometrial cancer. EGF transcript levels were marginally higher in endometrioid than non-endometrioid tumors (P=0.050), and in grade I compared to grade II tumors (P=0.053).

CONCLUSIONS

Up-regulation as well as down-regulation of EGF, IGF-1 and FGF2 transcript levels is observed in endometrial cancer; however IGF-1 and EGF down-regulation and FGF2 up-regulation seem to comprise the main features of endometrial carcinogenesis. The disruption of their mRNA co-expression pattern observed supports the hypothesis of a cross-talk between IGF- and EGF-mediated signaling pathways in promoting endothelial cell proliferation and differentiation in endometrial cancer.

摘要

背景

表皮生长因子和胰岛素样生长因子（EGF、IGFs）作为有丝分裂原，可促进内皮细胞增殖和分化。已有越来越多的证据表明EGF和IGF信号通路之间存在相互作用。成纤维细胞生长因子-2（FGF2）对多种细胞类型也有促有丝分裂作用，并与肿瘤血管生成和转移的调控有关。然而，在子宫内膜癌中，EGF、IGF-1和FGF2的转录水平鲜有研究。

方法

在本研究中，我们采用比较定量实时逆转录聚合酶链反应（RT-PCR）法，对30例子宫内膜癌标本及等量的相邻正常组织中EGF、IGF-1和FGF2的mRNA表达模式进行了评估。

结果

与相邻正常标本相比，子宫内膜癌中EGF、IGF-1和FGF2均有过表达和下调现象；然而，癌症的主要特征是IGF-1和EGF下调以及FGF2上调。在正常和恶性子宫内膜中，这三种因子呈现出不同的共表达模式。有趣的是，在子宫内膜癌中，FGF2 mRNA与EGF和IGF-1转录水平呈正相关（分别为P=0.024和P=0.006），而在相邻正常标本中未观察到共表达。此外，子宫内膜组织配对分析显示EGF和IGF-1之间存在显著正相关（P=0.010），支持了IGF和EGF介导的信号通路在子宫内膜癌中存在相互作用的假说。在子宫内膜样癌中，EGF转录水平略高于非子宫内膜样肿瘤（P=0.050），在I级肿瘤中高于II级肿瘤（P=0.053）。