Angiogenesis is a complex procedure induced by the secretion of numerous
growth factors from endothelial cells.
Vascular endothelial growth factor (
VEGF), basic fibroblastic
growth factor (
FGF2),
transforming growth factor-beta1, 2, 3 (TGFB1, 2, 3), and
transforming growth factor-beta receptors (
TGFBR1, 2, 3)
mRNA expression pattern was evaluated in tissue samples with
cervical intraepithelial neoplasia (CIN) and
cervical cancer, compared to that of normal cervical tissues, and correlated to the clinical stage of the disease. Transcript levels of the above genes were assessed by RT-PCR analysis in a total of 44 cervical specimens.
VEGF, TGFB1,
TGFBR1, and
FGF2 transcript levels were significantly different in the normal, CIN and
cancer specimen groups (P=0.015, 0.001, 0.008, and 0.029, respectively). Higher
TGFBR1 mRNA levels were observed in parallel with increased severity of the lesion, whereas
FGF2 exhibited lower transcript levels. A highly significant increase of
VEGF mRNA expression was found upon cervical neoplastic transformation (P<0.0001).
High-grade squamous intraepithelial lesions exhibited higher
VEGF mRNA levels than low-grade lesions (P=0.039).
TGFBR1 and
TGFBR3 receptors demonstrated significant co-expressions with TGFB2 (P<0.0001), and TGFB1 (P=0.005 and 0.002, respectively) in normal cervical specimens. However, a disruption of co-expression patterns was observed in the groups of CIN and
cancer cases, compared to normal tissues. Our findings show that
VEGF,
FGF2, TGFB1 and
TGFBR1 mRNA expression levels correlate with the malignant transformation of the uterine cervix. The involvement of the examined markers in cervical
carcinogenesis is furthermore supported by the observed disruption of their
mRNA co-expression patterns.