Expression of growth factors, growth factor receptors and apoptosis related proteins in invasive breast cancer: relation to apoptotic rate.

Abstract

To assess the relation between growth factors, growth-factor receptors, p53, bcl-2 and bax expression, and the rate of apoptosis in invasive breast cancer patients. Tumors from 45 patients were assessed by immunohistochemistry for expression patterns of five growth factors and their receptors; platelet-derived growth factor A chain (PDGF-AA) and PDGF-receptor alpha (PDGFalphaR), PDGF-BB and PDGFbetaR, transforming growth-factor alpha (TGFalpha) and its receptor-epidermal growth factor receptor (EGFR) and vascular-endothelial growth factor (VEGF) and its receptors vascular-endothelial growth factor receptor I (FLT-1) and vascular-endothelial growth factor receptor II (FLK-1/KDR), two growth-inhibiting factors; transforming-growth factor beta I (TGFbeta1) and TGFbeta2 and their receptor couple TGFbeta receptor I (TGFbetaR-I) and TGFbetaR-II, and basic-fibroblast growth factor (bFGF). Besides, the expression patterns of the bcl-2, bax and p53 gene products were investigated. Expression patterns were correlated to the number of apoptotic cells assessed by light microscopy. PDGF-BB and bFGF showed a positive correlation with the AI (p = 0.006 and p = 0.030, respectively). EGFR expression was associated with a high number of apoptotic cells but did not reach significance (p = 0.10). None of the other individual growth factors, growth-inhibiting factors or receptors showed a significant relation with the AI. The presence of a possible auto- or paracrine loop of the TGFalpha/EGFR combination was associated with a high number of apoptotic cells but did not reach significance (p = 0.20). PDGF-AA, bFGF and EGFR expression showed a significant relation to p53 overexpression. TGFbeta2 expression showed an inverse correlation with p53 overexpression. We found an association between several growth factors and growth-factor receptors with number of apoptotic cells. This underlines the importance of growth factors and their receptors not just in proliferation, but also, directly and/or indirectly, in regulating the rate of apoptosis in invasive breast cancer. Growth factors and their receptors may therefore be useful as targets of anti-cancer therapy by inducing apoptosis or increasing the sensitivity of cells for chemo- or hormonal therapy induced apoptosis.