[Correlation between transcriptional activity of vascular endothelial growth factor (VEFG) and transcriptional activity of its receptors (FLT-1 and FLK-1) in low-grade squamous intraepithelial lesions (LSIL) of uterine cervix].
OBJECTIVE
In this report we focus on angiogenesis, as one component of a complex molecular relations in the process of neovascularisation in the low-grade intraepithelial changes (LSIL). Increasing number of publications indicates that the interrelation between isoforms of VEGF (VEGF121, VEGF145, VEGF165, VEGF183, VEGF189, VEGF206) but not total VEGF is responsible for angiogenesis, both in physiological and pathological processes. The molecular co-operation of the said isoforms and their receptors results in morphological presentation of "de novo" created vascular network that dynamically involves the entire connective tissue stroma of the uterine cervix.


METHODS
The selection of intraepithelial pathology 38 cases to assess molecular activity of the given genes was based on colposcopy examination. Tissue specimens were taken for pathological investigation and to analyse transcriptional activity and mRNA alternative splicing of the angiogenesis genes. VEGF, Flt-1, Flk-1. To analyse quantitative gene expression RT-PCR TaqMan was performed. To estimate the dependence transcriptional activity of Flt-1 and Flk-1 on VEGF gene expression Spearman's correlation rank was performed. Differences with p < 0.05 were considered significant.


RESULTS
The comparison of transcriptional activity of VEGF and its receptors revealed significant correlation between increase in the number of Flt-1 mRNA copies and enhanced mRNA expression of VEGF121 (p < 0.05), VEGF145 (p < 0.05), VEGF165 (p < 0.05), VEGF183 (p < 0.05), VEGF189 (p < 0.05), and VEGF206 (p < 0.05). Significant increase in the number of Flk-1 mRNA copies was observed in case of enhanced mRNA expression of VEGF121 (p < 0.05), VEGF145 (p < 0.05), VEGF183 (p < 0.05), VEGF189 (p < 0.05) and VEGF206 (p < 0.05). The number of sFlt-1 mRNA copies significantly correlated only with enhanced VEGF145 mRNA expression (p < 0.05).


CONCLUSIONS
Changing intensification of transcriptional activity of VEGF gene and its receptors indicates on autocrine mechanism regulation of angiogenic genes activity in the first steep of carcinogenesis--LSIL.
Michalski
Bogdan
B
Katedry i Oddziału Klinicznego Ginekologii i Połoznictwa SlAM w Tychach.
Zieliński
Tomasz
T
Fila
Anna
A
Mazurek
Urszula
U
Poreba
Ryszard
R
Wilczok
Tadeusz
T
D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics*; D042442:Vascular Endothelial Growth Factors / Q000235:genetics*; D002578:Uterine Cervical Dysplasia / Q000737:chemistry* / Q000473:pathology
D012333:RNA, Messenger; D042442:Vascular Endothelial Growth Factors; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2