Transcriptional deregulation of VEGF, FGF2, TGF-beta1, 2, 3 and cognate receptors in breast tumorigenesis.
Angiogenesis is an important event during the neoplastic process and is induced by the secretion of numerous growth factors from endothelial cells. Vascular endothelial growth factor (VEGF), basic fibroblastic growth factor (FGF2), and transforming growth factor-beta1, beta2, beta3 (TGF-beta1, 2, 3) and cognate receptors (TGF-betaRI, II, III) mRNA expression pattern was evaluated by RT-PCR in 25 breast cancer tissue samples and adjacent normal tissues, and correlated to clinicopathological features. Western blot analysis was performed to evaluate VEGF and TGF-beta1 protein levels. TGF-beta1 and TGF-beta3 mRNA levels were significantly different in breast cancer specimens of differing histology (ductal, lobular, other) (P=0.020 and P=0.043). No statistically significant difference was observed at the mRNA level of VEGF between normal and tumor tissues while elevated VEGF protein levels in tumors were associated with patients' menopausal status. A strong hormonal influence of ER and PR on TGF-beta mRNA expression was established. FGF2 transcript levels were substantially decreased in cancer compared to adjacent normal specimens (P=0.031). A disruption of mRNA co-expression patterns was observed in malignant breast tissues compared to controls. Western blot analysis revealed differences between VEGF and TGFbeta1 mRNA and their corresponding protein levels. A substantial negative correlation of TGF-beta1 protein and TGF-beta1 mRNA levels (P=0.016) was demonstrated by breast tissue-pair analysis. Summarizing, our findings suggest that transcript levels of the examined markers in breast cancer are associated with menopausal and hormonal status, while their co-expression pattern is altered in malignant tissues compared to controls. In addition the difference between VEGF and TGF-beta1 mRNA and protein levels observed, indicates that post-transcriptional mechanisms may regulate expression of these molecules in breast cancer.
Soufla
Giannoula
G
Department of Virology, Medical School, University of Crete, P.O. Box 1527, Heraklion 710 03, Crete, Greece.
Porichis
Filippos
F
Sourvinos
George
G
Vassilaros
Stamatis
S
Spandidos
Demetrios A
DA
D000328:Adult; D000368:Aged; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism / Q000473:pathology; D018275:Carcinoma, Lobular / Q000378:metabolism / Q000473:pathology; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2; D053782:Transforming Growth Factor beta3; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism
D012333:RNA, Messenger; D012334:RNA, Neoplasm; D018125:Receptors, Transforming Growth Factor beta; C508960:TGFB1 protein, human; C509041:TGFB2 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2; D053782:Transforming Growth Factor beta3; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2