EXPRESSION OF VASCULAR ENDOTHELIAL GROWTH FACTOR AND ITS RECEPTORS IN BREAST CANCER

Objective:To clarify the role of VEGF and its receptors in breast tumor development.Methods:The mRNA expression of the four alternatively spliced VEGF isoforms (121,165,189 and 206 amino acids) and VEGF receptors (flt 1 and KDR) were examined by semiquantitative reverse transcriptase polymerase chain reaction analysis in breast cancer (29 specimens) and the corresponding adjacent non neoplastic breast tissues (29 specimens).Results:Three VEGF transcripts were detected in both malignant and non malignant breast tissues (121,165,189).The KDR transcripts and the two major VEGF transcripts (VEGF121 and VEGF165) were more abundant in breast carcinomas than in the adjacent non neoplastic breast tissues ( P 0.001). In contrast,the level of expression for flt 1 mRNA was not different in the malignant and the adjacent non neoplastic breast tissues ( P 0.5). Positive linear correlation was observed between VEGF and KDR in the breast carcinomas and adjacent non neoplastic breast tissues ( P 0.001, P 0.02). There was no linear correlation between VEGF and flt 1 expression ( P 0.1). VEGF121 mRNA expression level was significantly higher in premenopausal compared to post menopausal malignant breast tissues ( P 0.01).Conclusion:The intense expression of VEGF, KDR mRNA by breast carcinoma provides strong evidence linking VEGF expression to the angiogenesis associated with breast carcinoma. The positive linear correlation between VEGF expression and KDR expression clearly demonstrates VEGF induced up regulation of VEGF receptor. KDR is the main signaling receptor for VEGF in breast carcinoma, the VEGF/KDR system plays a functional role in the progression of breast carcinoma. Hormonal status can influence VEGF expression level in malignant breast tissues.