Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Keywords: RECEPTOR ; CANCER ; CELLS ; EXPRESSION ; GROWTH ; GROWTH-FACTOR ; CELL ; Germany ; human ; INHIBITION ; KINASE ; neoplasms ; PATHWAY ; SYSTEM ; SYSTEMS ; RISK ; GENE ; GENE-EXPRESSION ; PROTEIN ; transcription ; METABOLISM ; DIFFERENTIATION ; LINES ; ACTIVATION ; TRANSCRIPTION FACTOR ; BIOLOGY ; BREAST ; breast cancer ; BREAST-CANCER ; hormone ; ENCODES ; gene expression ; PROMOTER ; BRCA1 ; ovarian cancer ; OVARIAN-CANCER ; MUTATION ; LINE ; PATHOGENESIS ; SIGNALING PATHWAY ; MUTATIONS ; US ; transactivation ; CARCINOMAS ; RT-PCR ; FACTOR-I ; signaling ; IGF-I ; RE ; TRANSFECTION ; interaction ; GLAND ; development ; GROWTH-FACTOR-I ; Sp1 ; LEVEL ; CANCER DEVELOPMENT ; function ; INCREASED RISK ; OVARIAN ; mammary ; TRANSIENT TRANSFECTION ; GROWTH-FACTORS ; insulin-like growth factor-I ; GENE ENCODES ; IGF ; IGF-I receptor ; INSULIN-LIKE ; CONSEQUENCES ; IGFs
    Abstract: The insulin-like growth factors (IGFs) have a central role in mammary gland growth and differentiation as well as in breast cancer development. The BRCA1 gene encodes a pleiotropic protein that functions as a transcription factor. Germline BRCA1 mutations are associated with inherited predisposition to breast and ovarian cancer and confer a substantially increased risk for developing these neoplasms. Several lines of evidence led us to hypothesize that there is a functional interaction between the BRCA1 and IGF-I systems relevant to breast cancer biology. The present study tested the notion that BRCA1 gene expression is regulated by the IGF-I signaling pathway. Results of Western immunoblotting and RT-PCR analyses show that IGF-I stimulates BRCA1 protein and mRNA levels. Transient transfection experiments using BRCA1 promoter-luciferase reporter constructs reveal that IGF-I enhances BRCA1 promoter activity, suggesting that the effect of IGF-I is mediated at the transcriptional level. In addition, we provide evidence that the Sp1 zinc-finger protein is directly involved in BRCA1 gene transactivation. Combined, our data suggests that, at least part of the biological actions of IGF-I in mammary gland cells may be mediated through BRCA1. Dysregulated BRCA1 expression resulting from aberrant IGF signaling may have important consequences relevant to breast cancer pathogenesis
    Type of Publication: Journal article published
    PubMed ID: 17373631
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    Keywords: brain ; RECEPTOR ; EXPRESSION ; GROWTH ; evaluation ; Germany ; IN-VIVO ; MODEL ; MODELS ; PATHWAY ; PATHWAYS ; VIVO ; SUPPORT ; SYSTEM ; DISTINCT ; GENE ; GENE-EXPRESSION ; GENES ; PROTEINS ; transcription ; MICE ; ACTIVATION ; RESPONSES ; DNA ; TRANSCRIPTION FACTOR ; hepatocytes ; INTERVENTION ; MR ; BINDING ; MEMORY ; TARGET ; MOUSE ; TRANSCRIPTION FACTORS ; hormone ; IDENTIFICATION ; gene expression ; TRANSCRIPTIONAL ACTIVITY ; DISRUPTION ; MUTATION ; DISPLAY ; DNA-BINDING ; MUTATIONS ; US ; MOUSE MODEL ; glucocorticoid receptor ; BODY ; side effects ; RECEPTORS ; INSIGHTS ; CRE RECOMBINASE ; GLUCOCORTICOID-RECEPTOR ; REPRESSION ; DIMERIZATION ; immunosuppression ; DISSECTION ; steroid ; signaling ; targeting ; BODIES ; molecular ; RE ; INTERFERENCE ; RESOURCE ; regulation ; gene targeting ; GENE-REGULATION ; GENE-TRANSCRIPTION ; MOUSE MODELS ; TARGET GENE ; corticosteroid ; gene regulation ; mineralocorticoid receptor ; SI
    Abstract: Functional genomic technologies, including artificial chromosome-based transgenesis and conditional gene targeting, allowed us to generate mouse models harboring genes with loss-of-function mutations, gain-of-function mutations, spatially and/or temporally restricted mutations, tissue-specific mutations, and function-selective mutations. This kind of "allelic series" for corticosteroid receptors in mouse models provides a very useful resource for the molecular understanding of corticosteroid function in vivo. These models will also support the identification of steroid receptor target genes in order to define a steroid signaling cascade in molecular terms. They provide opportunities for the identification of compounds that regulate steroid receptors in a tissue-specific and function-selective manner. For example, selective glucocorticoid receptor modulators preventing receptor dimerization and DNA binding can be expected to reduce osteoporotic and/or diabetogenic side effects, but to display partial or full anti-inflammatory potential. Thus, these mouse models will help to evaluate distinct steroid receptor functions for therapeutic intervention.
    Type of Publication: Journal article published
    PubMed ID: 15241729
    Signatur Availability
    BibTip Others were also interested in ...
  • 3
    Keywords: EXPRESSION ; IN-VITRO ; Germany ; IN-VIVO ; INHIBITION ; THERAPY ; VITRO ; DISEASE ; DISEASES ; GENE ; GENE-EXPRESSION ; RNA ; MECHANISM ; STRATEGIES ; sensitivity ; TARGETS ; GENE-PRODUCT ; INTERFERENCE ; targeted ; adipose tissue ; BLOOD-GLUCOSE ; COACTIVATOR PGC-1 ; DIABETIC MICE ; GLUCONEOGENESIS ; hepatic glucose production ; HEPATIC GLUCOSE-PRODUCTION ; insulin signaling ; INSULIN-RESISTANCE ; metabolic syndrome ; renin-angiotensin-aldosterone system ; VISCERAL OBESITY
    Abstract: RNA interference is a naturally occurring cellular mechanism to inhibit the expression of specific gene products. The technical application of RNA interference offers great potential for the specific treatment of a huge variety of diseases including the metabolic syndrome, one of the most challenging threats to human health associated with our civilization. In order to develop novel and powerful strategies for the treatment of the metabolic syndrome, it is essential to define a set of specific gene products that may be targeted by RNA interference. Based on currently available in vitro and in vivo data, we discuss the feasibility of candidate genes involved in the pathophysiology of the metabolic syndrome as potential targets for a rational RNA interference based therapy in this review
    Type of Publication: Journal article published
    PubMed ID: 15778919
    Signatur Availability
    BibTip Others were also interested in ...
  • 4
    Keywords: Germany ; human ; MODEL ; COHORT ; RISK ; GENE ; ASSOCIATION ; polymorphism ; VARIANTS ; SEXUAL DIMORPHISM ; resistance ; WOMEN ; MEN ; OBESITY ; REDUCED RISK ; BODY ; TYPE-2 ; TRENDS ; DIETARY-FAT ; EPIC-GERMANY ; insulin ; MASS INDEX ; REGRESSION ; VARIANT ; INHERITANCE ; INSULIN-RESISTANCE ; metabolic syndrome ; GENDER ; BMI ; type 2 diabetes ; A54T polymorphism ; ABORIGINAL CANADIANS ; ALA54THR POLYMORPHISM ; FATTY-ACID-BINDING ; intestinal fatty acid binding protein ; POSTPRANDIAL RESPONSES ; PROTEIN-2 GENE
    Abstract: The T54 variant of the FABP2 gene has shown an association with the insulin resistance syndrome in some, but not all, studies. Here, we tested the hypothesis that the association between FABP2 A54T genotype and type 2 diabetes (T2DM) is confounded by body mass index (BMI) and is different between the two genders. 192 incident cases of T2DM and 384 sex- and age-matched controls were taken from the EPIC-Potsdam study cohort. Logistic regression analyses revealed that BMI was a strong confounder for diabetes risk association among women. When adjusted for BMI, the homozygous T54 variant was significantly associated with reduced risk of T2DM in women (OR = 0.24, 95%CI: 0.07-0.82), but not in men in the co-dominant inheritance model. Accordingly, HbA(1c) values were significantly lower in women carrying two T54 alleles with BMI regarded as covariate. While accounting for potentially confounding effects, linear trends of increased BMI and leptin values were observed in women according to the presence of T54 alleles. The interaction term (p = 0.04) of continuous BMI and T54-coding genotypes suggested that the T54 variant is an effect-modifier for BMI in females. We conclude that the T54 allele of FABP2 A54T is associated both with higher BMI and reduced risk of T2DM in women from the German EPIC-Potsdam study
    Type of Publication: Journal article published
    PubMed ID: 16718632
    Signatur Availability
    BibTip Others were also interested in ...
  • 5
    Keywords: CELLS ; EXPRESSION ; Germany ; COHORT ; POPULATION ; RISK ; PROTEIN ; ASSOCIATION ; LINKAGE ; polymorphism ; POLYMORPHISMS ; VARIANTS ; PROMOTER ; SNP ; OBESITY ; LINKAGE DISEQUILIBRIUM ; EPITHELIAL-CELLS ; cholesterol ; case-control studies ; BODY ; DIABETES-MELLITUS ; SMALL-INTESTINE ; TYPE-2 ; INITIATION ; case-control study ; VARIANT ; INCREASE ; SNPs ; LEVEL ; case control studies ; INSULIN-RESISTANCE ; BMI ; SUBSTITUTION ; type 2 diabetes ; LINKAGE-DISEQUILIBRIUM ; HUMAN CELL LINES ; ALA54THR POLYMORPHISM ; FATTY-ACID-BINDING ; PROTEIN-2 GENE ; PROMOTER POLYMORPHISMS ; ATCC STOCKS ; CODON-54 ; fatty acid-binding protein ; SEAP assay
    Abstract: Fatty acid-binding protein 2 (FABP2) is a cytosolic protein expressed exclusively in epithelial cells of the small intestine. Some, albeit not conclusive, evidence indicates that the Thr-allele of FABP2 Ala54Thr polymorphism is associated with type 2 diabetes. More recently, common FABP2 promoter polymorphisms have shown association with postprandial increase of triglycerides, body composition and plasma lipid levels. Therefore, we reasoned that variants in the FABP2 promoter may also predispose to type 2 diabetes mellitus. In our Caucasian study population, we found three SNPs and three insertion-deletion polymorphisms that are in complete linkage disequilibrium defining promoter haplotype A and B within 1kb5' of the FABP2 initiation codon. Haplotype calculations indicated that the FABP2 promoter and Ala54Thr variants were strongly linked. Functional analysis of promoter fragments demonstrated that haplotype difference is caused by polymorphisms within 260 bp downstream of the FABP2 initiation codon. Using a prospective case-control study nested within the EPIC-Potsdam cohort of 192 incident type 2 diabetes cases and 384 sex-/age-matched controls, male subjects carrying the FABP2 haplotype B allele showed significantly decreased risk of type 2 diabetes when adjusted for BMI (OR = 0.50, 95% CI = 0.28-0.87, p 〈 0.05) and additional covariates (OR = 0.42, 95% CI 0.22-0.81, p 〈 0.01). Further adjustment for the Ala54Thr polymorphism revealed an OR of 0.18 (95% CI 0.06-0.49, p 〈 0.001). Similarly, Ala/Ala homozygote males carrying the promoter haplotype B had decreased risk (0.33, 0.11-0.94, p 〈 0.05) of type 2 diabetes after stratification for the Ala54Thr polymorphism. FABP2 promoter haplotypes or genotype combinations defined by the promoter and Ala54Thr polymorphism were not associated with BMI, body fat, leptin, HbA(1c), total cholesterol or HDL. In conclusion, our findings suggest that the functional FABP2 promoter haplotype may contribute to type 2 diabetes in a sex-specific manner
    Type of Publication: Journal article published
    PubMed ID: 16718625
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...