title: VEGF, FGF2, TGFB1 and TGFBR1 mRNA expression levels correlate with the malignant transformation of the uterine cervix.
abstract: 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.
authors.affiliation: Laboratory of Virology, Medical School, University of Crete, P.O. Box 1527, Heraklion, 710 03 Crete, Greece.
authors.forename: Giannoula
authors.initials: G
authors.lastname: Soufla
authors.forename: Stavros
authors.initials: S
authors.lastname: Sifakis
authors.forename: Stavroula
authors.initials: S
authors.lastname: Baritaki
authors.forename: Alexandros
authors.initials: A
authors.lastname: Zafiropoulos
authors.forename: Eugenios
authors.initials: E
authors.lastname: Koumantakis
authors.forename: Demetrios A
authors.initials: DA
authors.lastname: Spandidos
mesh_terms: D030201:Activin Receptors, Type I / Q000235:genetics*; D000328:Adult; D002584:Cervix Uteri / Q000378:metabolism; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger / Q000378:metabolism; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000235:genetics*; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2; D002583:Uterine Cervical Neoplasms / Q000235:genetics*; D042442:Vascular Endothelial Growth Factors / Q000235:genetics*; D002578:Uterine Cervical Dysplasia / Q000235:genetics*
chemical_list: D012333:RNA, Messenger; 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; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625841:TGFBR1 protein, human