Document Detail

Growth regulation of prostatic stromal cells by prostate-specific antigen.
MedLine Citation:
PMID:  10511594     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Prostate-specific antigen (PSA) is a serine protease that can cleave insulin-like growth factor-binding protein-3 (IGFBP3), thereby decreasing its affinity for insulin-like growth factor-I (IGF-I). Dissociation of the IGF-I-IGFBP3 complex renders IGF-I available to bind to its receptor and stimulates cellular proliferation. We evaluated the potential for PSA to modulate the effects of IGF-I and IGFBP3 on the proliferation of human benign prostatic hyperplasia (BPH)-derived fibromuscular stromal cells in primary cultures. METHODS: We cultured BPH-derived stromal cells for 48 hours in serum-free RPMI-1640 medium supplemented with 0.2% bovine serum albumin and studied the effects of IGF-I, IGFBP3, PSA, and ZnCl(2) at varying concentrations. Differences in cell growth between control and treated cultures were evaluated by use of Dunnett's test. Concentration-related trends were evaluated by linear regression of log-transformed concentrations of test reagents on BPH-derived stromal cell number responses. Statistical tests were two-sided. RESULTS: We observed a concentration-dependent proliferative response of BPH-derived stromal cells to IGF-I. IGFBP3 inhibited this response in a concentration-dependent fashion. IGFBP3 alone had no effect on stromal cell proliferation. When stromal cells were incubated with PSA alone or with PSA, IGF-I, and IGFBP3, an increase in stromal cell numbers that was dependent on PSA concentration was evident in both instances. Zinc, an endogenous inhibitor of PSA enzymatic activity, was able to attenuate the stimulatory effect of PSA at intraprostatic physiologic concentrations. CONCLUSIONS: These results are consistent with the idea that PSA can modulate in vitro interactions between IGF-I and IGFBP3 and suggest that PSA may play a role in the regulation of human prostatic fibromuscular cell growth.
D M Sutkowski; R L Goode; J Baniel; C Teater; P Cohen; A M McNulty; H M Hsiung; G W Becker; B L Neubauer
Related Documents :
826064 - Tissue culture of isolated pancreatic islets.
9407164 - Increased synergistic effect of egf and igf-i on dna synthesis of cultured psoriatic ke...
12093114 - Cloning, characterization, and comparative activity of turbot igf-i and igf-ii.
6375004 - Survival of human fetal pancreatic explants in organ culture as reflected in insulin se...
2753164 - Effect of phenobarbital on the expression of glutathione s-transferase isoenzymes in cu...
10571964 - Seasonal response of carp (cyprinus carpio) ovarian cells to stimulation by various hor...
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of the National Cancer Institute     Volume:  91     ISSN:  0027-8874     ISO Abbreviation:  J. Natl. Cancer Inst.     Publication Date:  1999 Oct 
Date Detail:
Created Date:  1999-10-28     Completed Date:  1999-10-28     Revised Date:  2009-01-08    
Medline Journal Info:
Nlm Unique ID:  7503089     Medline TA:  J Natl Cancer Inst     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1663-9     Citation Subset:  IM    
Lilly Research Laboratories, a Division of Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Cell Division
Cells, Cultured
Chlorides / metabolism*
Chymotrypsin / metabolism
Insulin-Like Growth Factor Binding Protein 3 / metabolism*
Insulin-Like Growth Factor I / metabolism*
Prostate / growth & development*,  metabolism*
Prostate-Specific Antigen / metabolism*
Prostatic Hyperplasia / metabolism*
Recombinant Proteins / metabolism
Zinc Compounds / metabolism*
Reg. No./Substance:
0/Chlorides; 0/Insulin-Like Growth Factor Binding Protein 3; 0/Recombinant Proteins; 0/Zinc Compounds; 67763-96-6/Insulin-Like Growth Factor I; 7646-85-7/zinc chloride; EC 3.4.21.-/alpha-chymotrypsin; EC; EC Antigen

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Tamoxifen therapy for breast cancer and endometrial cancer risk.
Next Document:  Human leukocyte antigen class I gene mutations in cervical cancer.