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  • 1
    Keywords: RECEPTOR ; APOPTOSIS ; CANCER ; CELLS ; EXPRESSION ; GROWTH ; IN-VITRO ; tumor ; BLOOD ; CELL ; Germany ; KINASE ; TYROSINE KINASE ; VITRO ; incidence ; RISK ; GENE ; PROTEIN ; cell line ; DIFFERENTIATION ; TUMORS ; LINES ; PATIENT ; MESSENGER-RNA ; FAMILY ; DONOR ; BINDING ; CELL-LINES ; ASSOCIATION ; FREQUENCY ; polymorphism ; POLYMORPHISMS ; VARIANTS ; FREQUENCIES ; BREAST ; breast cancer ; BREAST-CANCER ; ASSAY ; DESIGN ; MOBILITY ; PROMOTER ; colorectal cancer ; COLORECTAL-CANCER ; mass spectrometry ; CELL-LINE ; LINE ; cancer risk ; REGION ; MASS-SPECTROMETRY ; MIGRATION ; MULTIVARIATE ; LIQUID-CHROMATOGRAPHY ; cell lines ; AFFINITY ; ESTROGEN-RECEPTOR ; MASSES ; ONCOLOGY ; REGRESSION ; RE ; VARIANT ; ALLELE ; regulation ; GENE PROMOTER ; REPORTER GENE ; interaction ; INTERVAL ; ASSAYS ; CELL-DIVISION ; GENOTYPE ; BREAST-TUMORS ; USA ; odds ratio ; cancer research ; RISK-FACTOR ; population-based ; CANCER-RISK ; colorectal ; receptor tyrosine kinase ; RECEPTOR TYROSINE KINASES ; case control ; LOGISTIC-REGRESSION ; DIVISION ; GENETIC-VARIATION ; binding affinity ; COLORECTAL TUMORS
    Abstract: Purpose:The receptor tyrosine kinase ERBB4/HER4 plays a role in cell division, migration, differentiation, as well as apoptosis, and is frequently overexpressed in breast and colorectal tumors. To understand the role of genetic variations in the regulation of ERBB4 expression, we identified new polymorphisms and investigated their functional implication and risk association with breast and colorectal cancer. Experimental Design: We screened colorectal tumors from 92 patients for genetic variants at the ERBB4 ATG -1000 bp 5'-regulatory region by denaturing high-performance liquid chromatography and sequencing. Variants were subjected to DNA-protein interaction analyses (electrophoretic mobility shift assay), reporter gene assays in breast cancer cell lines MDA134 and MDA157, and immunohistochemical analyses of breast tumors. We established genotype frequencies within a breast cancer case-control collection (1,021 cases, 1,015 population-based controls) and a colorectal cancer case-control collection (459 cases, 569 blood donors) using matrix-assisted laser desorption ionization/time of flight mass spectrometry. Adjusted odds ratios (OR) and 95% confidence intervals (Cl) were assessed by multivariate logistic regression. Results: We identified five new germ line variants -815 A 〉 T -782 G 〉 T, -638 insTC, -267 C 〉 G, and -219 del10bp. Two variants showed in vitro functional effects. The -782T allele showed lower protein binding affinity and lower promoter activity compared with the -782G allele, however, the -815T allele showed higher protein binding affinity and higher promoter activity. The -782T variant was identified as a risk allele for breast and colorectal cancer (OR, 1.59; 95% Cl, 1.06-2.34 and OR, 2.21; 95% Cl, 1.22-3.99, respectively). Conclusion: The ERBB4 -782 G 〉 T polymorphism, by virtue of its in vitro functional implication and incidence, is a risk factor for breast and colorectal cancer
    Type of Publication: Journal article published
    PubMed ID: 18094435
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  • 2
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Journal of Chromatography A 591 (1992), S. 367-370 
    ISSN: 0021-9673
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1777
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Analysis of the human expressed sequence tag (EST) database identified four clones that contain sequences of previously uncharacterized genes, members of the ATP-binding cassette (ABC) superfamily. Two new ABC genes (EST20237, 31252) are located at Chromosome (Chr) 1q42 and 1q25 respectively in humans, as determined by FISH; at locations distinct from previously mapped genes of this superfamily. Two additional clones, EST 600 and EST 1596, were found to represent different ATP-binding domains of the same gene, ABC2. This gene was localized to 9q34 in humans by FISH and to the proximal region of Chr 2 in mice by linkage analysis. All genes display extensive diversity in sequence and expression pattern. We present several approaches to characterizing EST clones and demonstrate that the analysis of EST clones from different tissues is a powerful approach to identify new members of important gene families. Some drawbacks of using EST databases, including chimerism of cDNA clones, are discussed.
    Type of Medium: Electronic Resource
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