Here we describe the development of a stable and reproducible ganitumab-resistant VCaP human prostate cancer cell derivative termed VCaP/GanR to investigate the mechanism of acquired resistance to IGF-1R inhibition.
Several growth factors, such as insulin-like growth factor 1 (IGF1), can induce AR activation, whereas insulin resistance and hyperinsulinemia are correlated with an elevated incidence of prostate cancer.
Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by unconditional logistic regression to determine the association between prostate cancer and IGF1 haplotypes and genotypes.
Decreased protein intake and body mass index, and increased physical activity and fruit and vegetable intake, following a prostate cancer diagnosis were associated with reduced post-diagnosis serum IGF-I and IGFBP-3.
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).
Deficiency in androgens and upregulation of insulin-like growth factor-1 are involved in high bone turnover in men receiving androgen deprivation therapy for prostate cancer.
IGF-1 elevation led to the accumulation of FOXO3A in the cytosol of prostate tumor cells and downregulation of its target gene Bim, which resulted in the apoptosis inhibition and prostate cancer overgrowth.
These data suggested that TGFbeta1, uPA, and IGF-I mediate at least in part cell-cell interactions and GR function in PA-III prostate cancer and UMR 106 osteosarcoma cells.
Stimulation of the prostate cancer cell line PC3 with IGF-1 induces a delayed phosphorylation of MET at multiple sites (indicative of full activation), reaching a maximum 18 hr after IGF-1 addition.
In this report, we offer evidence that a critical support of IGF-I in prostate cancer is mediated by its ability to suppress BMP4-induced apoptosis and Smad-mediated gene expression.
Prediagnostic IGF1 (HRhighest vs lowest quartile = 0.71; 95% CI = 0.48 to 1.04) and IGFBP3 (HR = 0.93; 95% CI = 0.65 to 1.34) levels were not associated with PCa mortality.
The risk of prostate cancer increased across quartiles of IGF-I (highest vs. lowest quartile, OR = 2.34; 95% CI = 1.26-4.34; p(trend) = 0.02) and IGF-II (OR = 1.78; 95% CI = 0.94-3.15; p(trend) = 0.09).
The present observations strongly suggest that AR activation may stimulate prostate cancer progression through the altered IGF-IR expression and IGF action.
Of these 14 genes only 6 (Cip1, IGF-1, NK4, CXCL 12, ILGF2R, RHOE) have already been associated with PCa, whereas the other 8 genes (FSTL-1, SOCS-2, Midkine, Thrombospondin 1, Secretory leukocyte protease inhibitor, Desmoglein 2, MLT 1, PTPRF) had not been previously related to PCa.
These mice offer an animal model for prostate cancer that will allow study of the stepwise development of this disease and the mechanism(s) whereby IGF-1 mediates this process.
Specimens of benign prostatic hypertrophy (BPH) and prostate carcinoma and prostate cells in culture were assessed for their capacity to bind androgens, radioiodinated EGF, and IGF-I, and to express certain cellular protooncogenes.
This study investigated the effects of lanreotide and new mono- and bi-specific SRIF agonists on proliferation, ligand-driven SRIF receptor (sst) dimerization and secretory pattern of the IGF system in LNCaP cells, a model of androgen-dependent PCa.LNCaP expressed all sst(s), but sst(4).
These findings suggest that variation in or around CYP17 and/or IGF1 may be associated with prostate cancer development in the African-American population.
The authors found no strong evidence that associations between GWAS-identified SNPs and prostate cancer are modified by circulating concentrations of IGF-1, sex hormones, or their major binding proteins.
We tested whether varying dietary carbohydrate and fat, without energy restriction relative to comparison diets, would slow tumor growth and reduce serum insulin, IGF-I, and other molecular mediators of prostate cancer in a xenograft model.
Recent research has outlined the association of circulating IGF-1 and prostate cancer risk, and studies have elucidated the implication of the IGF network in the early stages of prostate carcinogenesis.