Expression of keratinocyte growth factor and its receptor in human breast cancer: its inhibitory role in the induction of apoptosis possibly through the overexpression of Bcl-2

Keratinocyte growth factor (KGF), a mesenchymal cell derived paracrine growth factor that regulates normal epithelial cell proliferation, appears to be an essential mediator of steroids in various reproductive organs. The present study was designed to determine the expression and role of KGF and its receptor (KGFR) in human breast carcinoma tissues by immunohistochemistry. We also compared the results with the expression of estrogen receptor alpha (ERalpha), ERbeta, the proliferative activity assessed by the labeling index (LI) for the Ki-67 antigen, apoptotic frequency assessed by terminal dUTP nick end-labeling TUNEL) index, and the expression of Bcl-2. All of KGF-positive cases were ERalpha-positive (p<0.05), but not that of ERbeta, while all of KGFR-positive cases were ERbeta-positive (p<0.05), but not that of ERalpha. The specimens with the coexpression of KGF and KGFR significantly correlated with a lower TUNEL index (p<0.05), but not with Ki-67 LI in breast cancer tissues. Further analysis at the cellular level revealed that Bcl-2 was colocalized in KGFR-positive cells, and these cells were almost negative for TUNEL staining. Bcl-2-positive cells were also associated with ERbeta, as expected. Therefore, the results indicate that ERalpha may be involved in KGF expression, and that the coexpression of KGF and KGFR may play an inhibitory role in the induction of apoptosis possibly through the up-regulation of Bcl-2 expression in human breast cancer.