keratin 8 OKDB#: 4307
 Symbols: KRT8 Species: human
 Synonyms: K8, KO, CK8, CK-8, CYK8, K2C8, CARD2,K8, KO, CK8, CYK8, K2C8, CARD2,  Locus: 12q13 in Homo sapiens


For retrieval of Nucleotide and Amino Acid sequences please go to: OMIM Entrez Gene
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General Comment

NCBI Summary: This gene is a member of the type II keratin family clustered on the long arm of chromosome 12. Type I and type II keratins heteropolymerize to form intermediate-sized filaments in the cytoplasm of epithelial cells. The product of this gene typically dimerizes with keratin 18 to form an intermediate filament in simple single-layered epithelial cells. This protein plays a role in maintaining cellular structural integrity and also functions in signal transduction and cellular differentiation. Mutations in this gene cause cryptogenic cirrhosis. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2012]
General function Cytoskeleton
Comment
Cellular localization Cytoskeleton
Comment
Ovarian function Luteinization
Comment Estrous cycle-dependent changes of Fas expression in the bovine corpus luteum: influence of keratin 8/18 intermediate filaments and cytokines. Duncan A et al. ABSTRACT: BACKGROUND: Fas expression and Fas-induced apoptosis are mechanisms attributed to the selective destruction of cells of the corpus luteum (CL) during luteal regression. In certain cell-types, sensitivity to these death-inducing mechanisms is due to the loss or cleavage of keratin-containing intermediate filaments. Specifically, keratin 8/18 (K8/K18) filaments are hypothesized to influence cell death in part by regulating Fas expression at the cell surface. METHODS: Here, Fas expression on bovine luteal cells was quantified by flow cytometry during the early (Day 5, postovulation) and late stages (Days 16--18, postovulation) of CL function, and the relationship between Fas expression, K8/K18 filament expression and cytokine-induced cell death in vitro was evaluated. RESULTS: Both total and cell surface expression of Fas on luteal cells was greater for early versus late stage bovine CL (89% vs. 44% of cells for total Fas; 65% vs.18% of cells for cell surface Fas; respectively, P<0.05, n=6-9 CL/stage). A similar increase in the steady-state concentration of mRNA for Fas, as detected by quantitative real-time polymerase chain reaction, however, was not observed. Transient disruption of K8/K18 filaments in the luteal cells with acrylamide (5 mM), however, had no effect on the surface expression of Fas (P>0.05, n=4 CL/stage), despite evidence these conditions increased Fas expression on HepG2 cells (P<0.05, n= 3 expts). Exposure of the luteal cells to cytokines induced cell death (P<0.05) as expected, but there was no effect of K8/K18 filament disruption by acrylamide (P>0.05) or stage of CL (P>0.05, n= 4 CL/stage) on this outcome. CONCLUSION: In conclusion, we rejected our null hypothesis that the cell surface expression of Fas does not differ between luteal cells of early and late stage CL. The results also did not support the idea that K8/K18 filaments influence the expression of Fas on the surface of bovine luteal cells. Potential downstream effects of these filaments on death signaling, however, remain a possibility. Importantly, the elevated expression of Fas observed on cells of early stage bovine CL compared to late stage bovine CL raises a provocative question concerning the physiological role(s) of Fas in the corpus luteum, particularly during early luteal development.
Expression regulated by
Comment
Ovarian localization Luteal cells, Surface epithelium
Comment Marker profile of different phases in the transition of normal human ovarian epithelium to ovarian carcinomas. van Niekerk CC et al. To investigate whether early changes in the transformation of normal ovarian epithelial cells into tumor cells can be detected with monoclonal antibodies, a comparative immunohistochemical study was performed on normal human ovarian mesothelial cells, cystomas, cystadenomas, ovarian carcinomas, as well as granulosa cell tumor. Using monoclonal antibodies against different keratin subtypes, it was shown that mesothelial cells, ovarian cysts, cystadenomas, and carcinomas all reacted positively with broad-spectrum anti-keratin monoclonal antibodies (MAbs), as well as with MAbs to keratins 7, 8, 18, and 19. Keratins 4 and 13 were not found in mesothelial cells, but positive groups of cells were identified in several cystomas, adenomas, and carcinomas. While mesothelial cells did not react with the pan-epithelial marker BW495/36, invaginating metaplastic mesothelial cells, inclusion cysts, cystomas, adenomas, and carcinomas showed an increasing reactivity with BW495/36, with an increasing degree of malignancy. The reactivity of MAbs against ovarian carcinoma-associated antigens (OV-TL 3, OC 125, MOv 18, and OV-TL 10) was limited to weak staining reaction in some mesothelial cells but were found to be positive on more than 50% of the ovarian cystadenomas and more than 90% of the ovarian carcinomas. Thecal and granulosa cells of primordial, primary, and secondary follicles all reacted positively with antibodies to the broad-spectrum keratins OV-TL 12/5 and RCK 102, and to keratins 8 and 18, but not with keratins 4, 7, 13, and 19. These keratins decreased or disappeared in granulosa cells of mature follicles (Graafian follicles), whereas granulosa cell tumors did not react with anti-keratin antibodies. The reactivity of BW 495/36 was negative or limited to traces in some granulosa cells. Ovarian carcinoma-associated antigens were not expressed in granulosa cells or granulosa cell tumors. The data indicate that mesothelial cells undergoing metaplastic changes finally resulting in ovarian cystadenomas (and carcinomas) initiate the synthesis of a 200-kd glycoprotein recognized by MAb (BW 495/36), the production of ovarian carcinoma associated antigens, in addition to focal production of keratin 4 and/or 13, as seen in several samples. The granulosa cell tumors decrease or switch off their keratin production and remain negative for the 200-kd glycoprotein and the ovarian carcinoma-associated antigens. Expression and distribution of cytokeratin 8/18 intermediate filaments in bovine antral follicles and corpus luteum: an intrinsic mechanism of resistance to apoptosis? Townson DH et al. Apoptosis is a mechanism of cell elimination during follicular atresia and luteal regression. Recent evidence suggests sensitivity to apoptosis in some cell types is partly dependent upon cytokeratin-containing intermediate filaments. Specifically, cytokeratin 8/18 (CK8/18) filaments are thought to impart resistance to apoptosis. Here, cytokeratin filament expression within bovine ovarian follicles and corpora lutea (CL) was characterized and the potential relationship between cell-specific CK8/18 expression and apoptosis explored. Immunoprecipitation and western blot analysis confirmed CK8 associates with CK18 to form CK8/18 heterodimeric filaments within bovine ovarian cells. Immunostaining revealed populations of CK18-positive (CK18+) cells in healthy growing follicles that increased in postovulatory follicles. Atretic follicles at all stages of atresia also contained some CK18+ cells. However, no CK18+ cells were detected in primordial or primary follicles. In CL, developing CL contained a higher proportion of CK18+ cells (approximately 35%, range 30-70%) than mature CL (approximately 16%) and regressing CL (approximately 5%; P<0.05, n = 3-5 CL/stage), suggesting CK8/18 filament expression diminishes over time, as luteal cells become more susceptible to apoptosis. Dual-fluorescence labeling for CK18 and a cell death marker (TUNEL labeling) confirmed this view, demonstrating less death of CK18+ than CK18- luteal cells throughout the estrous cycle (P<0.05). The results indicate differential expression of CK8/18 filaments occurs in cells of bovine ovarian follicles and CL throughout the estrous cycle. The prevalence and cell-specific pattern of cytokeratin expression in these structures is consistent with the concept these filaments might impart resistance to apoptosis in ovarian cells as is seen in other cell types.
Follicle stages Secondary, Antral, Corpus luteum
Comment Characterization and Significance of Adhesion and Junction-Related Proteins in Mouse Ovarian Follicles. Mora JM et al. In the ovary, initiation of follicle growth is marked by cuboidalization of flattened granulosa cells (GCs). The regulation and cell biology of this shape change remains poorly understood. We propose that characterization of intercellular junctions and associated proteins is key to identifying as yet unknown regulators of this important transition. As GCs are conventionally described as epithelial, this study used mouse ovaries and isolated follicles to investigate epithelial junctional complexes (tight junctions [TJ], adherens junctions [AJ] and desmosomes) and associated molecules, as well as classic epithelial markers by quantitative PCR and immunofluorescence. These junctions were further characterized using ultrastructural, calcium-depletion and biotin tracer studies. Junctions observed by transmission electron microscopy between GCs and between GCs and the oocyte were identified as AJs by expression of N-cadherin and nectin 2, and by lack of TJ and desmosome-associated proteins. Follicles were also permeable to biotin confirming a lack of functional TJs. Surprisingly, GCs lacked all epithelial markers analysed, including E-cadherin, cytokeratin 8, and zonula occludens (ZO)-1alpha+. Furthermore, vimentin was expressed by GCs suggesting a more mesenchymal phenotype. In calcium-free conditions, small follicles maintained oocyte-GC contact confirming the importance of calcium-independent nectin at this stage. However, in primary and multilayered follicles, lack of calcium resulted in loss of contact between GCs and oocyte, showing that nectin alone cannot maintain attachment between these two cell types. Lack of classic markers suggests that GCs are not epithelial. Identification of AJs during GC cuboidalization highlights the importance of AJs in regulating initiation of follicle growth.
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created: 2010-06-02 06:48:41 by: Aaron J Hsueh, hsuehlab   email: aaron.hsueh@stanford.edu
home page: http://reprobio.stanford.edu/hsueh
last update: 2012-11-13 10:43:32 by: Aaron J Hsueh, hsuehlab   email: aaron.hsueh@stanford.edu



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