Influence of Bicalutamide with or without Tamoxifen or Anastrozole on Insulin-like Growth Factor 1 and Binding Proteins in Prostate Cancer Patients

2006 ◽  
Vol 21 (2) ◽  
pp. 123-126 ◽  
Author(s):  
F. Boccardo ◽  
A. Rubagotti ◽  
M. Battaglia ◽  
F. Zattoni ◽  
A. Bertaccini ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Binding Proteins ◽  
Binding Protein ◽  
Sharp Decrease ◽  
Serum Levels ◽  
Inhibitory Influence ◽  
Concurrent Administration ◽  
Protein Levels ◽  
Pharmacological Medication ◽  
Igfbp 3

Background There is growing evidence that IGF-1 and binding proteins may be involved in prostate cancer promotion and progression. Patients and methods IGF-1 and binding proteins (IGFBP-1 and 3) serum levels were measured at baseline and after 3 and 6 months of treatment in a selected group of patients with prostate cancer who were randomly assigned to treatment with bicalutamide, bicalutamide plus anastrozole or bicalutamide plus tamoxifen in a comparative study investigating the role of pharmacological medication in the development of bicalutamide-induced gynecomastia. Results Bicalutamide monotherapy does not appear to alter the IGF-1/IGFBP system. In fact, the increase in IGF-1 levels induced by this treatment was paralleled by comparable increases in binding protein (IGFBP-3). No major changes from baseline up to month 6 either in IGF-1 or in IGFBP-1 and 3 were observed in the bicalutamide plus anastrozole arm. The addition of tamoxifen to bicalutamide produced a sharp decrease in IGF-1 levels (p<0.001) coupled with an increase in both IGFBP-1 (p=0.001) and, to a lesser extent, IGFBP-3 (p=0.5). Conclusions The concurrent administration of tamoxifen and bicalutamide reduces the synthesis and bioavailability of IGF-1. Moreover, increased binding protein levels might exert antiproliferative and proapoptotic effects on prostate cancer cells, independently of the IGF-1/IGF receptor-mediated survival system. Both effects might have a synergistic inhibitory influence on prostate cancer growth.

scholarly journals Differential Activation of the IGF Binding Protein-3 Promoter by Butyrate in Prostate Cancer Cells

Endocrinology ◽  
2002 ◽  
Vol 143 (5) ◽  
pp. 1778-1788 ◽  
Author(s):  
Junko Tsubaki ◽  
Vivian Hwa ◽  
Stephen M. Twigg ◽  
Ron G. Rosenfeld
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Binding Protein ◽  
Luciferase Reporter ◽  
Lncap Cells ◽  
Prostate Cancer Cells ◽  
Protein Levels ◽  
Igf Binding ◽  
Igf Binding Protein ◽  
Igfbp 3

Abstract Sodium butyrate (NaB), a dietary micronutrient, is a potent growth inhibitor that initiates cell differentiation in many cell types, including prostate cancer cells. The molecular mechanisms by which these effects occur remain largely unknown. In this study, we investigated the effects of NaB on the expression of IGF binding protein (IGFBP)-3, a known growth regulator, in two human prostate cancer cell lines (PC-3 and LNCaP). Treatment with NaB (0–10 mm) caused a dose-dependent stimulation of IGFBP-3 mRNA expression and parallel increases in protein levels. A specific histone deacetylase inhibitor, trichostatin A (TSA) similarly induced IGFBP-3 expression, indicating that histone hyperacetylation may be critical in the regulation of IGFBP-3 expression. To investigate the molecular mechanism of NaB-regulated IGFBP-3 expression, 1.87 kb of the human IGFBP-3 gene promoter was cloned into the pGL2-basic luciferase reporter vector. In both PC-3 and LNCaP cells, NaB (10 mm) significantly increased luciferase activity 20- to 30-fold, compared with the untreated control. However, using 5′ sequential deletion constructs of the IGFBP-3 promoter, the NaB response sequences in the IGFBP-3 promoter were different in PC-3 and LNCaP cells. Our studies identified a region, −75 to +69 from the start of transcription (+1), that is fully inducible by NaB treatment in LNCaP cells, but not in PC-3 cells. Unlike other well characterized NaB-regulated genes, Sp1 DNA sequences are not involved in NaB up-regulation of IGFBP-3 gene in LNCaP cells. Further deletion studies identified two independent regions critical for NaB-induced transactivation in LNCaP cells. These regions contain consensus binding sites for p53 and GATA, respectively, but mutational analyses and gel shift assays suggested that, while the p53 response element is required for NaB responsiveness, neither p53 nor GATA are involved. In summary, we have demonstrated that 1) NaB significantly up-regulates IGFBP-3 mRNA and protein levels in PC-3 and LNCaP prostate cancer cells; and 2) novel butyrate- responsive elements lacking consensus Sp1 sites are used in LNCaP cells.

scholarly journals Insulin-like growth factor-binding protein-3 is partially responsible for high-serum-induced apoptosis in PC-3 prostate cancer cells

1999 ◽  
Vol 163 (3) ◽  
pp. 487-494 ◽  
Author(s):  
R Rajah ◽  
A Khare ◽  
PD Lee ◽  
P Cohen
Keyword(s):  
Prostate Cancer ◽  
Binding Protein ◽  
High Serum ◽  
Apoptotic Index ◽  
Serum Concentrations ◽  
Induction Of Apoptosis ◽  
Induced Apoptosis ◽  
Dose Dependent ◽  
Igfbp 3

Cells are known to undergo apoptosis when cultured in high serum concentrations. However, the serum factors responsible for this induction of apoptosis have not been identified. The IGF-binding protein-3 (IGFBP-3), a negative growth regulator, is found at concentrations of 5 microgram/ml in serum. We have recently demonstrated that IGFBP-3 induces apoptosis in PC-3 cells, a prostate cancer cell line, at a concentration of 500 ng/ml. In this communication, we demonstrate the role of IGFBP-3 as one of the apoptosis-inducing agents in high serum concentrations. Treatment of PC-3 cells with increasing concentrations (40% to 90%) of intact human serum (HS) resulted in a dose-dependent decrease in cell growth. Valinomycin, an ionophore, was used as a positive control to measure the induction of apoptosis by serum treatment in PC-3 cells. Treatment with 90% serum showed significant suppression of growth (P<0.001) compared with the effect of 10% serum. Treatment with increasing concentrations of HS (40% to 90%) resulted in a dose-dependent increase in apoptosis. Treatment with 90% HS showed a 10-fold increase in apoptotic index compared with cells treated with 10% HS. Treatment of PC-3 cells with IGFs and IGFBP-3-depleted 90% human sera (depleted serum=DS) demonstrated significantly lower levels of apoptosis (50% reduction in the effect of 90% HS) suggesting a role of IGFBP-3 in inducing apoptosis in high serum concentration. Furthermore, treatment with DS supplemented with recombinant IGFBP-3 (500 ng/ml) brought the apoptotic index down close to the level of apoptosis induced by 90% intact serum treatment (P<0.001). However, DS supplemented with physiological concentrations of IGFs (500 ng/ml) showed only partial recovery of cell survival demonstrated by 90% DS. This data indicates that IGFBP-3 is one of the factors in serum that is responsible for high-serum-induced apoptosis.

Serum levels of insulin-like growth factors (IGF-I and IGF-II) and their binding protein (IGFBP-3) are not elevated in pancreatic cancer

1997 ◽  
Vol 22 (2) ◽  
pp. 95-100
Author(s):  
James D. Evans ◽  
Margaret C. Eggo ◽  
Ian A. Donovan ◽  
Simon R. Bramhall ◽  
John P. Neoptolemos
Keyword(s):  
Pancreatic Cancer ◽  
Growth Factors ◽  
Binding Protein ◽  
Serum Levels ◽  
Igf I ◽  
Igfbp 3 ◽  
Insulin Like Growth Factors

scholarly journals Investigation of insulin-like growth factors/insulin-like growth factor binding proteins regulation in metabolic syndrome patients

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Somayeh Pouriamehr ◽  
Haleh Barmaki ◽  
Mozhdeh Rastegary ◽  
Farzaneh Lotfi ◽  
Mohsen Nabi Afjadi
Keyword(s):  
Metabolic Syndrome ◽  
Growth Factors ◽  
Binding Proteins ◽  
Negative Relationship ◽  
Serum Levels ◽  
Control Group ◽  
Cholesterol Levels ◽  
Potential Biomarker ◽  
Igfbp 3 ◽  
Insulin Like Growth Factors

Abstract Objective The insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) are thought to play a significant role in metabolic pathways and glucose metabolism. Unregulated levels of IGFs/IGFBPs have been associated with the development of glucose intolerance and metabolic syndrome X (MSx). We hypothesized that change of IGFs/IGFBPs levels could increase the risk of MSx; thus, this study aimed to evaluate the serostatus of IGFs/IGFBPs in individuals with MSx. Results After adjustment for metabolic parameters, MSx patients had a lower level of IGF-1, IGFBP-1, and IGFBP-2 compared with subjects in the control group. Further analysis revealed a positive correlation between serum levels of IGF-1 and IGF-2 (p < 0.05), as well as serum IGFBP-3 and IGF-2 (p < 0.05). Also, the statistical analysis showed a negative association of serum IGF-1 with plasma glucose and total cholesterol levels (p < 0.05). Besides, a negative relationship was found between serum concentrations of IGF-1/IGF-2 and the risk of developing MSx. These data indicated that some components of IGFs/IGFBPs are linked with the pathogenesis of MSx. In conclusion, these inverse associations showed a possible linkage between the IGF/IGFBP signaling pathway and the development of MSx. It seems the decreased concentrations of IGFs edmay be regarded as a potential biomarker for early diagnosis or even prognosis of MSx but need more systematic studies to confirmed it.

scholarly journals Effect of Therapy with Recombinant Human Growth Hormone on Insulin-Like Growth Factor System Components and Serum Levels of Biochemical Markers of Bone Formation in Children After Severe Burn Injury1

1998 ◽  
Vol 83 (1) ◽  
pp. 21-24 ◽  
Author(s):  
Gordon L. Klein ◽  
Steven E. Wolf ◽  
Craig B. Langman ◽  
Clifford J. Rosen ◽  
Subburaman Mohan ◽  
...  
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Bone Formation ◽  
Binding Protein ◽  
Serum Levels ◽  
Controlled Study ◽  
Type I ◽  
Insulin Like Growth Factor ◽  
Type I Procollagen ◽  
Igfbp 3

Burn injury in children is associated with low bone formation and long-term bone loss. Because recombinant human GH (rHGH) may accelerate burn wound healing, and because rHGH increases bone formation and density in GH-deficient patients, we studied the short-term effects of rHGH on bone formation, reflected by osteocalcin and type I procollagen propeptide levels in a randomized, double-blind, placebo-controlled study. Nineteen patients were enrolled and received either rHGH (0.2 mg/kg·day) or an equal volume of saline. Mean burn size and age were not different between the groups, and test substances were given from admission to time of wound healing (mean: 43 ± 22 days). At wound healing, serum levels of insulin-like growth factor (IGF)-1 and IGF binding protein (IGFBP)-3 in the rHGH group rose to mean values of 229% and 187% of the respective means of the placebo group (P &lt; 0.025). Serum osteocalcin concentrations remained below normal in both groups, and type I procollagen propeptide levels achieved a low normal level. IGFBP-4 levels were twice that of normal on admission and doubled further at wound healing; IGFBP-5 levels were low on admission but rose to normal at wound healing. We conclude that large doses of rHGH were ineffective in improving disordered bone formation despite increasing serum IGF-1 and IGFBP-3. The rHGH-independent rise in serum levels of the inhibitory binding protein IGFBP-4 suggests a mechanism by which improved bone formation is prevented despite successful elevation of IGF-1 and IGFBP-3 in the burned child.

scholarly journals Protein QTL analysis of IGF-I and its binding proteins provides insights into growth biology

2020 ◽  
Author(s):  
Eric Bartell ◽  
Masanobu Fujimoto ◽  
Jane C. Khoury ◽  
Philip R. Khoury ◽  
Sailaja Vedantam ◽  
...  
Keyword(s):  
Birth Weight ◽  
Association Studies ◽  
Genetic Regulation ◽  
Human Growth ◽  
Serum Levels ◽  
Genome Wide Association Studies ◽  
Genetic Associations ◽  
Protein Levels ◽  
Igf I ◽  
Igfbp 3

AbstractThe growth hormone and insulin-like growth factor (IGF) system is integral to human growth. Genome-wide association studies (GWAS) have identified variants associated with height and located near the genes in this pathway. However, mechanisms underlying these genetic associations are not understood. To investigate the regulation of the genes in this pathway and mechanisms by which regulation could affect growth, we performed GWAS of measured serum protein levels of IGF-I, IGFBP-3, PAPP-A2, IGF-II, and IGFBP-5 in 839 children (3-18 years) from the Cincinnati Genomic Control Cohort. We identified variants associated with protein levels near IGFBP3 and IGFBP5 genes, which contain multiple signals of association with height and other skeletal growth phenotypes. Surprisingly, variants that associate with protein levels at these two loci do not colocalize with height associations, confirmed through conditional analysis. Rather, the IGFBP3 signal (associated with total IGFBP-3 and IGF-II levels) colocalizes with an association with sitting height ratio (SHR); the IGFBP5 signal (associated with IGFBP-5 levels) colocalizes with birth weight. Indeed, height-associated SNPs near genes encoding other proteins in this pathway are not associated with serum levels, possibly excluding PAPP-A2. Mendelian randomization supports a stronger relationship of measured serum levels with SHR (for IGFBP-3) and birth weight (for IGFBP-5) than with height. In conclusion, we begin to characterize the genetic regulation of serum levels of IGF-related proteins in childhood. Furthermore, our data strongly suggest the existence of growth-regulating mechanisms acting through IGF-related genes in ways that are not reflected in measured serum levels of the corresponding proteins.

Serum levels of insulin-like growth factor-1 and insulin-like growth factor binding protein-3 in relapsing and primary progressive multiple sclerosis

2005 ◽  
Vol 11 (1) ◽  
pp. 13-15 ◽  
Author(s):  
N Wilczak ◽  
G SM Ramsaransing ◽  
J Mostert ◽  
D Chesik ◽  
J De Keyser
Keyword(s):  
Multiple Sclerosis ◽  
Growth Factor ◽  
Disease Duration ◽  
Binding Protein ◽  
Serum Levels ◽  
Progressive Multiple Sclerosis ◽  
Primary Progressive Multiple Sclerosis ◽  
Insulin Like Growth Factor ◽  
Primary Progressive ◽  
Igfbp 3

Using radioimmunoassay we measured serum levels of insulin-like growth factor (IGF)-1 and IGF binding protein (IGFBP)-3 in patients with relapsing multiple sclerosis (MS) and a benign course (Expanded Disability Status Scale (EDSS)≤ 3 despite > 10 years disease duration), relapsing MS with cumulative disability leading to an EDSS score > 4 within 10 years of disease duration, primary progressive MS and healthy controls. We found no differences in IGF-1 and IGFBP-3 serum levels, and the IGF-1/IGFBP-3 ratio between the four groups. However, there was a significant correlation (P=0.005) between IGFBP-3 serum levels and both the progression index of disability and the Multiple Sclerosis Severity Score in patients with primary progressive MS.

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