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An Orthotopic Murine Model of Human Prostate Cancer Metastasis
Published on: September 18, 2013
Prostatic involution in men taking finasteride is associated with elevated levels of insulin-like growth
L N Thomas1, A S Wright, C B Lazier
1Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada. lnthomas@is.dal.ca
Background:
Insulin-like growth factor-binding proteins (IGFBPs)-2, -4, and -5 are associated with upregulation of apoptosis in the ovary. The purpose of this study was to assess the roles of IGF-I and IGFBPs during involution of the prostate. Frozen and fixed tissue was collected by transurethral prostatectomy from Caucasian men, aged 52-82 years, scheduled for prostatectomy for benign prostatic hyperplasia, who took either placebo (n = 7) or the 5alpha-reductase inhibitor finasteride for 6 days to 6 years (n = 15) prior to surgery.
Methods:
Intraprostatic androgen levels were measured by radioimmunoassay. Tissues were immunostained for IGF-I and IGFBP-2, -3, -4, and -5, and staining was quantitated by computerized image analysis. Serial sections were stained for markers of apoptosis (TUNEL and tissue transglutaminase) and IGFBP-2, -4, or -5.
Results:
IGF-I staining was significantly decreased in the medium-term (18-43 days) treatment group and remained so for the duration of the study (P = 0.026). IGFBP-3 staining was unchanged in the early and medium-term treatment groups; however, a transient earlier rise in the level of this proapoptotic protein cannot be ruled out. The percentage of epithelial cell area staining positively for IGFBP-2 increased significantly, from 1.6 +/- 0.5 in the placebo group to 12.0 +/- 2.0 (P < 0.0001), and 7.6 +/- 1.9 (P = 0.003) in the short (6-13 days) and medium-term treatment groups, respectively. IGFBP-4 staining increased from 2.2 +/- 0.6 to 9.8 +/- 1.9 (P < 0.0001) and 7.4 +/- 1.2 (P = 0.004) in the short and medium-term groups, respectively, and IGFBP-5 staining increased from 0.2 +/- 0.1 to 3.8 +/- 2.0 (P = 0.004) in the medium-term group. The results from serial sections showed that IGFBP-2 and -4 costained with markers of apoptosis, while IGFBP-5 did not.
Conclusions:
These results indicate that IGFBP-2, -4, and -5 are associated with prostatic involution. Because of the timing and distribution of expression, we hypothesize that IGFBP-2 and -4 have a role as signals for apoptosis, but that IGFBP-5 likely does not.
Insights
Insulin-like growth factor-binding proteins (IGFBPs)-2 and -4 signal apoptosis during prostate involution. IGFBP-5 is not associated with apoptosis, despite increased levels with finasteride treatment.
Area of Science:
- Endocrinology
- Cell Biology
- Urology
Background:
- Insulin-like growth factor-binding proteins (IGFBPs) are implicated in apoptosis.
- Previous studies linked IGFBPs-2, -4, and -5 to ovarian apoptosis.
Purpose of the Study:
- To investigate the roles of IGF-I and IGFBPs in prostate involution.
- To assess the effects of finasteride on these proteins in the prostate.
Main Methods:
- Tissue samples were collected from men undergoing prostatectomy.
- Immunohistochemistry was used to quantify IGF-I and IGFBP levels.
- Apoptosis markers were analyzed alongside IGFBP expression.
Main Results:
- IGFBP-2 and IGFBP-4 expression significantly increased with finasteride treatment and co-localized with apoptosis markers.
- IGFBP-5 levels also increased but did not co-localize with apoptosis.
- IGF-I levels decreased, while IGFBP-3 remained unchanged.
Conclusions:
- IGFBP-2 and IGFBP-4 are likely involved in signaling apoptosis during prostate involution.
- IGFBP-5 does not appear to play a role in apoptosis despite altered expression patterns.
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