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Expression and cellular localization of keratinocyte growth factor and its receptor in human hyperplastic prostate
A De Bellis1, C Crescioli, C Grappone
1Department of Clinical Physiopathology, University of Florence, Italy.
Abstract:
It is well recognized that the actions of androgens alone do not explain the hyperplastic development of the gland that occurs in elderly men. The increasing number of reports confirming the lack of mitogenic activity of androgens coupled with the powerful mitogenic activity of growth factors and the discovery of growth factor receptors led to an increased interest in the putative role of growth factors in prostate physiopathology. We have previously demonstrated the presence and the cellular localization of epidermal growth factor and of the related peptide, transforming growth factor-alpha, together with their common receptor in the epithelial compartment of the human hyperplastic prostate tissue (BPH). In the present study we examined the expression and cellular localization of messenger ribonucleic acid (RNA) encoding keratinocyte growth factor (KGF) and its receptor in human hyperplastic prostate tissue. RT-PCR of total RNA extracted from BPH tissues documented the presence of transcripts for KGF and its receptor. In situ hybridization with specific RNA probes synthesized from the respective complementary DNA demonstrated that KGF mRNA was mainly localized in the stromal cells, whereas its receptor was mainly localized in the prostate epithelium. Moreover, the mitogenic activity of KGF on cultured BPH cells compared to that of other growth factors has been tested. Our findings clearly indicate that KGF has the ability to function as a potent mitogen in BPH cells. Our data support the hypothesis that KGF plays an important role in prostate growth and that in human prostate it seems to act in a paracrine fashion.
Insights
Keratinocyte growth factor (KGF) acts as a potent mitogen in benign prostatic hyperplasia (BPH) cells. This suggests KGF plays a significant role in prostate growth, potentially acting in a paracrine manner.
Area of Science:
- Urology
- Endocrinology
- Molecular Biology
Background:
- Androgens alone do not fully explain prostate hyperplasia in elderly men.
- Growth factors and their receptors are increasingly implicated in prostate physiopathology.
- Epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-α) are present in human hyperplastic prostate tissue.
Purpose of the Study:
- To investigate the expression and localization of keratinocyte growth factor (KGF) and its receptor in human benign prostatic hyperplasia (BPH) tissue.
- To assess the mitogenic activity of KGF on BPH cells.
Main Methods:
- Reverse transcription-polymerase chain reaction (RT-PCR) to detect KGF and its receptor mRNA.
- In situ hybridization to determine the cellular localization of KGF mRNA and its receptor.
- In vitro testing of KGF's mitogenic activity on cultured BPH cells.
Main Results:
- Transcripts for KGF and its receptor were detected in BPH tissues.
- KGF mRNA was primarily found in stromal cells, while its receptor was localized in the prostate epithelium.
- KGF demonstrated potent mitogenic activity on cultured BPH cells.
Conclusions:
- KGF is expressed in human BPH tissue and acts as a potent mitogen for BPH cells.
- KGF likely plays a significant role in prostate growth.
- In the human prostate, KGF appears to function via a paracrine mechanism.