Insulin-like growth factor-I produced by seminal vesicles: relationship to intraepithelial basal cell hyperplasia in the prostate.
OBJECTIVE
This study examined the seminal vesicle fluid (SVF) as a potential local source of insulin-like growth factor-I (IGF-I) in the peripheral zone of the prostate.


METHODS
IGF-I levels in seminal fluid were measured. The levels of the IGF-I receptor (IGF-IR) in its active, phosphorylated form as well as direct downstream targets were examined in the peripheral zone of the prostate.


RESULTS
In situ, we find that the IGF-IR is activated in the peripheral zone in areas of atrophy, prostatic intraepithelial hyperplasia, and cancer. In addition, immunostaining reveals preferential activation of the IGF-IR in p63-positive cells in areas of intermediate basal cell hyperplasia in the peripheral zone, indicating that prostate progenitor cells are highly sensitive to increases in local IGF-I levels. These areas of basal cell hyperplasia occur at high incidence in the peripheral zone of the prostate. Relatively high levels of IGF-I were identified in SVF. In addition, we find that SVF can stimulate the proliferation of both normal and cancer-derived prostate cells.


CONCLUSIONS
These results suggest that SVF is a local source of IGF-I that provides chronic stimulation of prostate cells. This chronic stimulation could contribute to the development of prostate cancer in older men.
Garcia
Fernando U
FU
Department of Pathology, Drexel University College of Medicine, Philadelphia, PA 19102, USA. Fernando.Garcia@DrexelMed.edu
Urbanska
Katarzyna
K
Koltowski
Lauren
L
Reiss
Krzysztof
K
Sell
Christian
C
D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005786:Gene Expression Regulation; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000502:physiology*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D010766:Phosphorylation; D011467:Prostate / Q000378:metabolism; D011470:Prostatic Hyperplasia / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D012669:Seminal Vesicles / Q000378:metabolism*; D015398:Signal Transduction
C081876:CKAP4 protein, human; D008565:Membrane Proteins; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1