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- Fagman, Henrik, 1975, et al.
(författare)
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Nuclear accumulation of full-length and truncated adenomatous polyposis coli protein in tumor cells depends on proliferation.
- 2003
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Ingår i: Oncogene. - : Springer Science and Business Media LLC. - 0950-9232 .- 1476-5594. ; 22:38, s. 6013-22
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Tidskriftsartikel (refereegranskat)abstract
- The adenomatous polyposis coli (APC) tumor suppressor is a nucleocytoplasmic protein. The nuclear accumulation of APC was recently found to vary depending on cell density, suggesting that putative APC function(s) in the nucleus is controlled by the establishment of cell contacts. We report here that the density-dependent redistribution of APC between nucleus and cytoplasm prevails in 6/6 thyroid and colorectal carcinoma cell lines. Moreover, mutated APC lacking known nuclear localization sequences had the similar distribution pattern as the full-length protein. APC invariably accumulated in the nuclei of Ki-67 expressing cells, but was largely cytoplasmic when cell cycle exit was induced by serum starvation or at high cell density. APC colocalized with beta-catenin in the nucleus only in one cell line (SW480). Also, APC maintained a predominantly nuclear position in early confluent states when cytoplasmic beta-catenin was recruited to newly formed adherens-like junctions. The results indicate that nuclear targeting of APC is driven by cell cycle entry rather than altered cell-cell contact. The ability of C-terminally truncated APC to accumulate in the nucleus suggests that nuclear import signals other than NLS1(APC) and NLS2(APC) are functionally important. Residual function(s) of N-terminal APC fragments in tumor cells carrying APC mutations might be beneficial to tumor growth and survival.
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- Kanter-Smoler, Gunilla, et al.
(författare)
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Clinical characterization and the mutation spectrum in Swedish adenomatous polyposis families
- 2008
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Ingår i: BMC Medicine. - : BioMed Central. - 1741-7015. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Background: The dominantly inherited condition familial adenomatous polyposis (FAP) is caused by germline mutations in the APC gene. Finding the causative mutations has great implications for the families. Correlating the genotypes to the phenotypes could help to improve the diagnosis and follow-up of patients.Methods: Mutation screening of APCand the clinical characterization of 96 unrelated FAP patients from the Swedish Polyposis Registry was performed. In addition to generally used mutation screening methods, analyses of splicing-affecting mutations and investigations of the presence of low-frequency mutation alleles, indicating mosaics, have been performed, as well as quantitative real-time polymerase chain reaction to detect lowered expression of APC.Results: Sixty-one different APC mutations in 81 of the 96 families were identified and 27 of those are novel. We have previously shown that 6 of the 96 patients carried biallelic MUTYH mutations. The 9 mutation-negative cases all display an attenuated or atypical phenotype. Probands with a genotype (codon 1250-1464) predicting a severe phenotype had a median age at diagnosis of 21.8 (range, 11-49) years compared with 34.4 (range, 14-57) years among those with mutations outside this region (P < 0.017). Dense polyposis (> 1000) occurred in 75% of the probands with a severe phenotype compared with 30% in those with mutations outside this region. The morbidity in colorectal cancer among probands was 25% at a mean age of 37.5 years and 29% at a mean age of 46.6 years.Conclusion: Using a variety of mutation-detection techniques, we have achieved a 100% detection frequency in classical FAP. Probands with APC mutations outside codon 1250-1464, although exhibiting a less-severe phenotype, are at high risk of having a colorectal cancer at diagnosis indicating that age at diagnosis is as important as the severity of the disease for colorectal cancer morbidity. © 2008 Kanter-Smoler et al; licensee BioMed Central Ltd.
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- Lindfors, Lina, et al.
(författare)
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Is GPR146 really the receptor for proinsulin C-peptide?
- 2020
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Ingår i: Bioorganic & Medicinal Chemistry Letters. - : Elsevier. - 0960-894X .- 1464-3405. ; 30:13
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Tidskriftsartikel (refereegranskat)abstract
- Proinsulin C-peptide has previously been proposed to interact with a G-protein coupled receptor (GPCR), specifically the orphan receptor GPR146. To investigate the potential of C-peptide in treating complications of diabetes, such as kidney damage, it is necessary to understand its mode of action. We used CHO-K1 cells expressing human GPR146 to study human and murine C-peptide in dynamic mass redistribution and GPCR beta-arrestin assays, as well as with fluorescence confocal microscopy. Neither assay revealed any significant intracellular response to C-peptide at concentrations of up to 33 mu M. We observed no internalisation of C-peptide by fluorescence microscopy. Our results do not support GPR146 as the receptor for C-peptide, but suggest that further investigations of the mode of action of C-peptide should be undertaken.
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| 5. |
- Messing, Maria, et al.
(författare)
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Generation of Pd Model Catalyst Nanoparticles by Spark Discharge
- 2010
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Ingår i: Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 114:20, s. 9257-9263
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Tidskriftsartikel (refereegranskat)abstract
- We present a method to deposit Pd nanoparticles with a very small size distribution by an aerosol process onto oxide substrates for the creation of model systems in catalytic research. The Pd nanoparticles are characterized by transmission electron microscopy, scanning electron microscopy, X-ray photoelectron spectroscopy, and X-ray diffraction. We confirm the small size dispersion from the desired particle size, and we show that the particle surface coverage can he highly controlled. Further, our measurements indicate that an amorphous shell surrounding a crystalline core of the Pd particles may form during the particle synthesis and that the shell contains carbon.
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| 7. |
- Meuller, Johan, et al.
(författare)
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Identification of genomic deletions of the APC gene in familial adenomatous polyposis by two independent quantitative techniques.
- 2004
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Ingår i: Genetic testing. - : Mary Ann Liebert Inc. - 1090-6576 .- 1557-7473. ; 8:3, s. 248-56
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Tidskriftsartikel (refereegranskat)abstract
- Large deletions in the APC (adenomatous polyposis coli) gene, causing familial adenomatous polyposis (FAP), cannot easily be detected by conventional mutation-detection techniques. Therefore, we have developed two independent quantitative methods for the detection of large deletions, encompassing one or more exons, of APC. Multiplex ligation-dependent probe amplification (MLPA) is performed in one reaction for the initial quantification of all APC exon copy numbers. Subsequently, quantitative real-time PCR (QRT-PCR) is used to verify the results obtained in the MLPA reaction. The identification of a deletion of the whole APC gene in a patient with classical FAP is described. The mutation was detected with the two quantitative methods and further verified on chromosomal level by the use of FISH (fluorescence in situ hybridization) on metaphase spreads. Furthermore, a large deletion covering exons 11-13 of the APC gene was detected in two apparently unrelated families. This deletion was further verified and characterized with long-range PCR. The MLPA test ensures a sensitive high-throughput screening for large deletions of the APC gene and can easily be implemented in the diagnostic testing for FAP.
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