Transcriptional deregulation of VEGF, FGF2, TGF-β1, 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- beta 1, beta 2, beta 3 (TGF-beta 1, 2, 3) and cognate receptors (TGF-beta R1, 11, 111) 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-beta 1 protein levels. TGF-beta 1 and TGF-beta 3 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 rnRNA co-expression patterns was observed in malignant breast tissues compared to controls. Western blot analysis revealed differences between VEGF and TGF beta 1 mRNA and their corresponding protein levels. A substantial negative correlation of TGF-beta 1 protein and TGF-beta 1 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-beta 1 mRNA and protein levels observed, indicates that posttranscriptional mechanisms may regulate expression of these molecules in breast cancer. (c) 2005 Elsevier Ireland Ltd. All rights reserved.