Transcriptome profiling of breast cancer cells with Insulin like growth factor binding protein 2 (IGFBP2) knockdown
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Sehgal P
PROVIDER: S-ECPF-GEOD-40682 | biostudies-other | 2013
REPOSITORIES: biostudies-other
Similar Datasets
Project description:The study was carried out to identify the genes regulated upon IGFBP2 modulation in breast cancer. This will help to understand the molecular targets and biological pathways targeted by IGFBP2 in breast cancer.
2013-09-06 | GSE40682 | GEO
Project description:The study was carried out to identify the genes regulated upon IGFBP2 modulation in breast cancer. This will help to understand the molecular targets and biological pathways targeted by IGFBP2 in breast cancer. C5 (Cy5) Vs. Vector(Cy3), C5 (Cy5) Vs. Vector(Cy3), C12 (Cy5) Vs. Vector(Cy3), C12 (Cy5) vs. Vector(Cy3)
2013-09-06 | E-GEOD-40682 | biostudies-arrayexpress
Project description:Obesity is associated epidemiologically with poor breast cancer prognosis, but the mechanisms remain unclear. Since IGF binding protein-3 (IGFBP-3) influences both breast cancer growth and adipocyte maturation, it may impact on how obesity promotes breast oncogenesis. This study investigated the role of endogenous IGFBP-3 on the development of obesity and subsequently on breast tumor growth. Wild-type (WT) C57BL/6 or IGFBP-3-null (BP3KO) mice were fed a high-fat diet (HFD) or control chow-diet for 15 weeks before orthotopic injection with syngeneic EO771 murine breast cancer cells. When the largest tumor reached 1000 mm3, tissues and tumors were excised for analysis. Compared to WT, BP3KO mice showed significantly reduced weight gain and mammary fat pad mass (contralateral to tumor) in response to HFD, despite similar food intake. EO771 tumor weight and volume were increased by HFD and decreased by BP3KO. Despite differences in tumor size, tumors in BP3KO mice showed no differences from WT in the number of mitotically active (Ki67+) and apoptotic (cleaved caspase-3+) cells, but had greater infiltration of CD3+ T-cells. These data suggest that endogenous (circulating and/or stromal) IGFBP-3 is stimulatory to adipose tissue expansion and enhances mammary tumor growth in immune-competent mice, potentially by suppressing T-cell infiltration into tumors.
| S-EPMC5342431 | biostudies-literature
Project description:BackgroundPrevious studies suggest a combined effect of insulin-like growth factor 1 (igf-1) and igf binding protein 3 (igfbp-3) gene polymorphisms, xenoestrogen, and phytoestrogen on the igf-1 signalling pathway and serum concentrations in the igf system, which are associated with premenopausal breast cancer (bca) risk.MethodsBetween 2010 and 2012, our study recruited 140 premenopausal bca patients and 160 community-based premenopausal control subjects. Participants were surveyed about oral contraceptive (oc) use, dietary habits, and other bca risk factors. TaqMan assays were used to determine igf-1 rs1520220 and igfbp-3 rs2854744 genotypes. Daily intakes of energy-adjusted soy isoflavones (easis) were calculated by the residual method. Multivariate logistic regression was applied to estimate the adjusted odds ratios (ors) and 95% confidence intervals (cis) of the igf-1 rs1520220 and igfbp-3 rs2854744 genotypes, oc use, and intake of easis. Stratified analyses were performed to detect the gene-environment combined effect, and multivariate logistic regression was used to estimate interaction coefficients (iors) by the multiplicative model, with 95% cis. The delta method was used to calculate interaction coefficients by the additive model [relative excess risk of interaction (reri), attributable proportions of interaction (apis)] and 95% cis.ResultsThe igf-1 and igfbp-3 genotypes, oc use, and easis were not found to be associated with bca risk (p > 0.05). Stratified analysis showed that the risk of bca was markedly increased in women carrying the igfbp-3C allele and using ocs compared with women either carrying the igfbp-3C allele or using ocs (or: 3.02; 95% ci: 1.04 to 8.79). The interaction coefficients ior, reri, and api were 4.89 (95% ci: 1.09 to 21.90), 2.42 (95% ci: -0.76 to 5.61), and 0.80 (95% ci: 0.46 to 1.67) respectively.ConclusionsThe igfbp-3 rs2854744 polymorphism and oc use might synergistically increase premenopausal bca risk.
| S-EPMC4754064 | biostudies-literature
Project description:AIM:To investigate the functional significance of insulin-like growth factor binding protein-5 (IGFBP-5) overexpression in pancreatic cancer (PaC). METHODS:The effects of IGFBP-5 on cell growth were assessed by stable transfection of BxPC-3 and PANC-1 cell lines and measuring cell number and DNA synthesis. Alterations in the cell cycle were assessed by flow cytometry and immunoblot analyses. Changes in cell survival and signal transduction were evaluated after mitogen activated protein kinase and phosphatidylinositol 3-kinase (PI3K) inhibitor treatment. RESULTS:After serum deprivation, IGFBP-5 expression increased both cell number and DNA synthesis in BxPC-3 cells, but reduced cell number in PANC-1 cells. Consistent with this observation, cell cycle analysis of IGFBP-5-expressing cells revealed accelerated cell cycle progression in BxPC-3 and G2/M arrest of PANC-1 cells. Signal transduction analysis revealed that Akt activation was increased in BxPC-3, but reduced in PANC-1 cells that express IGFBP-5. Inhibition of PI3K with LY294002 suppressed extracellular signal-regulated kinase-1 and -2 (ERK1/2) activation in BxPC-3, but enhanced ERK1/2 activation in PANC-1 cells that express IGFBP-5. When MEK1/2 was blocked, Akt activation remained elevated in IGFBP-5 expressing PaC cells; however, inhibition of PI3K or MEK1/2 abrogated IGFBP-5-mediated cell survival. CONCLUSION:These results indicate that IGFBP-5 expression affects the cell cycle and survival signal pathways and thus it may be an important mediator of PaC cell growth.
| S-EPMC2712896 | biostudies-literature
Project description:BACKGROUND:Epidemiological evidence supports a positive association between circulating insulin-like growth factor-1 (IGF-1) concentrations and breast cancer risk, but both the magnitude and causality of this relationship are uncertain. We conducted observational analyses with adjustment for regression dilution bias, and Mendelian randomization (MR) analyses allowed for causal inference. PATIENTS AND METHODS:We investigated the associations between circulating IGF-1 concentrations and incident breast cancer risk in 206 263 women in the UK Biobank. Multivariable hazard ratios (HRs) and 95% confidence intervals (CI) were estimated using Cox proportional hazards models. HRs were corrected for regression dilution using repeat IGF-1 measures available in a subsample of 6711 women. For the MR analyses, genetic variants associated with circulating IGF-1 and IGF-binding protein-3 (IGFBP-3) levels were identified and their association with breast cancer was examined with two-sample MR methods using genome-wide data from 122 977 cases and 105 974 controls. RESULTS:In the UK Biobank, after a median follow-up of 7.1 years, 4360 incident breast cancer cases occurred. In the multivariable-adjusted models corrected for regression dilution, higher IGF-1 concentrations were associated with a greater risk of breast cancer (HR per 5 nmol/l increment of IGF-1 = 1.11, 95% CI = 1.07-1.16). Similar positive associations were found by follow-up time, menopausal status, body mass index, and other risk factors. In the MR analyses, a 5 nmol/l increment in genetically-predicted IGF-1 concentration was associated with a greater breast cancer risk (odds ratio = 1.05, 95% CI = 1.01-1.10; P = 0.02), with a similar effect estimate for estrogen-positive (ER+) tumours, but no effect found for estrogen-negative (ER-) tumours. Genetically-predicted IGFBP-3 concentrations were not associated with breast cancer risk (odds ratio per 1-standard deviation increment = 1.00, 95% CI = 0.97-1.04; P = 0.98). CONCLUSION:Our results support a probable causal relationship between circulating IGF-1 concentrations and breast cancer, suggesting that interventions targeting the IGF pathway may be beneficial in preventing breast tumorigenesis.
| S-EPMC7221341 | biostudies-literature
Project description:The insulin-like growth factor-2 mRNA-binding protein 1 (IGF2BP1) plays essential roles in embryogenesis and carcinogenesis. IGF2BP1 serves as a post-transcriptional fine-tuner regulating the expression of some essential mRNA targets required for the control of tumor cell proliferation and growth, invasion, and chemo-resistance, associating with a poor overall survival and metastasis in various types of human cancers. Therefore, IGF2BP1 has been traditionally regarded as an oncogene and potential therapeutic target for cancers. Nevertheless, a few studies have also demonstrated its tumor-suppressive role. However, the details about the contradictory functions of IGF2BP1 are unclear. The growing numbers of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) have been identified as its direct regulators, during tumor cell proliferation, growth, and invasion in multiple cancers. Thus, the mechanisms of post-transcriptional modulation of gene expression mediated by IGF2BP1, miRNAs, and lncRNAs in determining the fate of the development of tissues and organs, as well as tumorigenesis, need to be elucidated. In this review, we summarized the tissue distribution, expression, and roles of IGF2BP1 in embryogenesis and tumorigenesis, and focused on modulation of the interconnectivity between IGF2BP1 and its targeted mRNAs or non-coding RNAs (ncRNAs). The potential use of inhibitors of IGF2BP1 and its related pathways in cancer therapy was also discussed.
| S-EPMC6025799 | biostudies-literature
Project description:The insulin and insulin like growth factor (IGF) signaling systems are implicated in breast cancer biology. Thus, disrupting IGF/insulin signaling has been shown to have promise in a number of preclinical models. However, human clinical trials have been less promising. Despite evidence of some activity in early phase trials, randomized phase III studies have thus far been unable to show a benefit of blocking IGF signaling in combination with conventional strategies. In breast cancer, combination anti IGF/insulin signaling agents with hormone therapy has not yet proven to have benefit. This inability to translate the preclinical findings into useful clinical strategies calls attention to the need for a deeper understanding of this complex pathway. Development of predictive biomarkers and optimal inhibitory strategies of the IGF/insulin system should yield better clinical strategies. Furthermore, unraveling the interaction between the IGF/insulin pathway and other critical signaling pathways in breast cancer biology, namely estrogen receptor-? (ER?) and epidermal growth factor receptor (EGFR) pathways, provides additional new concepts in designing combination therapies. In this review, we will briefly summarize the current strategies targeting the IGF/insulin system, discuss the possible reasons of success or failure of the existing therapies, and provide potential future directions for research and clinical trials.
| S-EPMC3534944 | biostudies-literature
Project description:Insulin-like growth factor binding protein-3 (IGFBP-3) is a vital protein exist in circulation which interacts with high affinity to insulin-like growth factor (IGFs) altering their activities. Therefore, the interaction between IGFs and IGFBP-3 has a key role altering large spectrum of activities such as cell cycle progression, proliferation and apoptosis. Despite decades of research, the crystal structure of IGFBP-3 has not been identified possibly due to some technical challenge in its crystallizing. The three-dimensional (3D) structure of IGFBP-3 was predicted using homology modeling, Phyre2, and molecular dynamic. Its interaction with IGF-1 was also identified by HADDOCK software. IGFBP-3 has the most identity with other IGFBPs in N and C-domain; however, its linker domain has lower identity. Our data predicted that IGF-1 structurally interacts with N-domain and linker domain of IGFBP-3. Some conserved residues of IGFBP-3 such as Glu33, Arg36, Gly39, Arg60, Arg66, Asn109, and Ile146 interacts with Glu3, Asp12, Phe16, Gly19, Asp20, Arg21, and Glu58 of IGF-1. In addition, our data predict that the linker domain has a loop structure which covers post translational modification and interacts with IGF-1. The phosphorylation of Ser111 in linker domain, which previously has been shown to induce apoptosis make a repulsive force interrupting this interaction to IGF-1, which enables IGFBP-3 to induce apoptosis. The present study suggests that the linker domain has a key role in recognition of IGFBP-3 with IGF-1.
| S-EPMC6040160 | biostudies-literature
Project description:1. evaluation of diagnostic importance of insulin like growth factor binding protein3 in patient with recently diagnosed as Colorectal cancer
2. correlation between the diagnostic efficacy of insulin like growth factor binding protein 3 with routine marker carcinoembryonic antigen.
| 59449 | ecrin-mdr-crc