INT232826
From wiki-pain
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Sentences Mentioned In
Key: | Protein | Mutation | Event | Anatomy | Negation | Speculation | Pain term | Disease term |
Figure 2I shows as an example the FACS-based quantitation of Krt18 expression in G-2 cells at passage 20, indicating transition towards a mesenchymal differentiation state. | |||||||||||||||
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In early passages the majority of the G-2 cells expressed both Krt14 (Figure 2G) and Krt18 intermediate filament proteins (Figure 2H); however the usual co-polymerization partner of Krt14, the Krt5 protein, was not detectable by a specific antibody (data not shown). | |||||||||||||||
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In subsequent passages slight variations in the individual expression levels of Krt14 and Krt18 (data not shown) and a significant fluctuation in the number of cytokeratin-expressing cells ranging from 40 to 70% were observed. | |||||||||||||||
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As visualized by IF-staining, the G-2 cell pattern of cytokeratin expression was reproduced in G-2 cell derived clones (Figure S1AB; shown as example for clones G-2C9 and G-2C11), although according to qPCR analysis the relative levels of Krt14 and Krt18 gene expression varied markedly between clones (Figure S1CD). | |||||||||||||||
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The few Thy1high cells expressing Krt18 may represent either contaminating cells, or cells which are in process of transition towards the Thy1low-state (see below). | |||||||||||||||
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Both OSE and EOC tumors are characterized by the expression of different keratins such as KRT7, KRT8 and KRT18. | |||||||||||||||
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Stronger expression of Krt7 is observed in TOV-1946 and TOV-2223G was the only cell line that expressed Krt18 and Krt8. | |||||||||||||||
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In order to determine if our cell lines presented these EOC markers, we monitored protein expression of Krt7, Krt8 and Krt18 by western blot. | |||||||||||||||
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The epithelial characteristics of the cell lines were also verified by the expression of Krt18 and Krt8, which are also markers of epithelial cells. | |||||||||||||||
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Several pathogenic mechanisms were implicated in this process (Fig. 4; Dobson 2004):1.Enhanced oxidative stress2.Disproportional K8/K18 expression together with keratin modifications3.Chaperone dysfunction4.Elevated p62 levels5.Insufficient protein degradation | |||||||||||||||
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MDBs also arise in cell culture after transfection with K8/K18, ubiquitin, and p62. | |||||||||||||||
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Keratins are major constituents of MDBs and both altered K8/K18 expression and keratin modification seems to affect MDB formation (Zatloukal et al. 2007; Ku et al. 2007). | |||||||||||||||
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Griseofulvin/DDC feeding leads to rapid induction of K8/K18 expression with disproportional K8 > K18 levels (Denk et al. 2000). | |||||||||||||||
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Dysbalanced K8/K18 expression precedes MDB formation, likely increases keratin misfolding and predisposes to posttranslational modifications, which may interfere with keratin refolding and/or repair. | |||||||||||||||
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However, one important caveat is the fact, that K8/K18/K19 are expressed in most simple epithelial cells and are therefore not liver-specific (Moll et al. 1982; Ku et al. 1999). | |||||||||||||||
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In cell culture experiments, protein aggregates resembling MDBs formed only after p62 co-transfection, but not when K8, K18, and ubiquitin were transfected alone or in combination (Stumptner et al. 2007). | |||||||||||||||
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Adult hepatocytes are unique among simple epithelial cells in that they express exclusively K8 and K18, whereas other glandular epithelia exhibit a more complex keratin expression pattern (Omary et al. 2002; Ku et al. 2007). | |||||||||||||||
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The K8/K18 within MDBs exhibit increased ? | |||||||||||||||
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For example, simple (i.e., single layered) epithelia, as found in digestive organs, express K8 together with variable levels of K7, K18, K19, and K20 depending on the tissue (Moll et al. 1982; Ku et al. 1999; Coulombe and Omary 2002; Ku et al. 2007). | |||||||||||||||
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The K8/K18 within MDBs exhibit increased ? | |||||||||||||||
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General Comments
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