FGF2 transcript levels are positively correlated with EGF and IGF-1 in the malignant endometrium.
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.
Soufla
Giannoula
G
Department of Virology, Medical School, University of Crete, PO Box 1527, Heraklion 71003, Crete, Greece.
Sifakis
Stavros
S
Spandidos
Demetrios A
DA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018269:Carcinoma, Endometrioid / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D015536:Down-Regulation; D016889:Endometrial Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D004717:Endometrium / Q000737:chemistry* / Q000473:pathology; D004815:Epidermal Growth Factor / Q000032:analysis* / Q000235:genetics; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000032:analysis* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis* / Q000235:genetics; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis*; D015854:Up-Regulation
D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I