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

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

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.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Endometrioid / chemistry*
  • Carcinoma, Endometrioid / genetics
  • Carcinoma, Endometrioid / pathology
  • Down-Regulation
  • Endometrial Neoplasms / chemistry*
  • Endometrial Neoplasms / genetics
  • Endometrial Neoplasms / pathology
  • Endometrium / chemistry*
  • Endometrium / pathology
  • Epidermal Growth Factor / analysis*
  • Epidermal Growth Factor / genetics
  • Female
  • Fibroblast Growth Factor 2 / analysis*
  • Fibroblast Growth Factor 2 / genetics
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Insulin-Like Growth Factor I / analysis*
  • Insulin-Like Growth Factor I / genetics
  • Middle Aged
  • Polymerase Chain Reaction
  • RNA, Messenger / analysis*
  • Up-Regulation

Substances

  • RNA, Messenger
  • Fibroblast Growth Factor 2
  • Epidermal Growth Factor
  • Insulin-Like Growth Factor I