Disease relevance of Krt2-8

• To address the possible physiological relevance of these observations, we transfected simple keratins (K8 and 18) either individually, or in combination, into a tumorigenic but non-metastatic pancreatic adenocarcinoma that expresses vimentin but no keratins [1].
• In this investigation, we demonstrate that a soluble form of CK 8 is released into the culture medium of breast cancer cell lines [2].
• Concomitantly, the differentiation status shifted from a keratinizing towards a non-keratinizing squamous carcinoma, which was further confirmed by the cytokeratin profile of the carcinoma (presence of CK 8, 10, 13, 14, 18, 19) [3].
• Polyoma virus middle T antigen (mT) transforms the T51B cell line and induces the loss of the cytokeratin 8 and 14 pair (CK8/CK14) present in these rat nonparenchymal liver epithelial cells (LECs), because of the selective down-regulation of CK14 gene expression [4].

High impact information on Krt2-8

• All SHs at day 10 immunocytochemically showed positivity for albumin, transferrin, CK8, and CK18, which are markers for hepatocytes [5].
• The cells produced albumin and displayed a cytokeratin (CK) pattern typical of hepatocytes (CK 8 and CK 18-positive and CK 19-negative) [6].
• No changes were observed in properties indicative of well-differentiated hepatocytes, including cellular morphology, ultrastructure, albumin, or cytokeratin-8 expression [7].
• All of the biliary epithelial cells and ductular hepatocytic cells exhibited a strongly positive immunohistochemical staining for gamma-glutamyl transpeptidase and for cytokeratin 8 [8].
• Intermediate filaments were also disrupted, as visualised by cytokeratin 8/18 immunocytochemistry [9].

Biological context of Krt2-8

• Keratin 8 phosphorylation in vitro by cAMP-dependent protein kinase occurs within the amino- and carboxyl-terminal end domains [10].
• Contrasting effects of K8 and K18 on stabilizing K19 expression, cell motility and tumorigenicity in the BSp73 adenocarcinoma [1].
• Immunofluorescence staining revealed that MT indeed induced an inhibition of CK14 gene expression and a loss of CK8/CK14 intermediate filaments (IFs) in liver cells, whereas ST and LT had no effect [11].
• From day 16 of gestation the pre-hepatocytes became desmin-negative, remained CK-8 and CK-18 positive [12].
• These data indicate that excessive expression of CK 8 mRNA is a characteristic of prostatic stem cells, and CK molecules are excellent markers for determining the hierarchical pathway of cell differentiation in prostate epithelium [13].

Anatomical context of Krt2-8

• At the onset of testicular differentiation, when the first Sertoli cells differentiate in the gonad of 13.5-day old male fetuses, positive staining for CK 18 became evident, in addition to CK 8 and CK 19 expression [14].
• In the trachea only CK7 expression changed, and in the lung expression of CK7 (bronchioli) and CK8 (bronchus) changed; the expression of other CK polypeptides did not change [15].
• K8 and KII mAbs labelled almost all epithelium, while K18 stained cortical epithelium and a subpopulation of medullary TEC [16].
• Among them a group of cytokeratin 8 and 18 specific monoclonal antibodies which stained the goblet cells as well as cytokeratin 8 and 18 positive internal controls did not react with either the cytokeratin 8 and 18 positive neuroectodermal cells of the rat eye nor the rat choroid plexus epithelium [17].
• In the basophilic hepatocyte foci, overexpression of cytokeratin 8 was consistently associated with cells organizing into acini, with expression reminiscent of authentic bile ducts, possibly indicating a structure-function relationship [18].

Associations of Krt2-8 with chemical compounds

• Phosphopeptide maps of keratins phosphorylated in vivo and in vitro indicate that Ca2+/calmodulin-dependent kinase may be involved in regulating the serine-specific phosphorylation of both keratin 8 and keratin 18, while cAMP-dependent protein kinase does not seem to play a major role in this context [19].
• Cx 32 expression was first observed between days 10-15 and colocalized to differentiated luminal cells (CK 8/18) [20].
• Cytokeratin 8 (CK 8) has been identified as a plasminogen-binding protein expressed on the external surfaces of hepatocytes and breast carcinoma cells [Hembrough, Vasudevan, Allietta, Glass and Gonias (1995) J. Cell Sci. 108, 1071-1082] [2].
• CK8 and C-3 show evidence of similar androgen regulation during development [21].
• Differential expression of c-erb B2/neu, epidermal growth factor receptor, cytokeratin 8, and the prostatic steroid-binding protein gene in rat ventral prostate during postnatal development [21].

Other interactions of Krt2-8

• Keratin 8 rather than keratin 18 was the major target of the kinase [10].
• Every colony consisted of cells that each had a single nucleus and a higher nucleus/cytoplasm ratio than surrounding hepatocytes, and immunocytochemically the cells induced by any mitogen were stained with albumin, transferrin, cytokeratin-8 and -18 [22].
• RESULTS: Two types of cell populations, a large single-cell population and a small single-cell population, were obtained and characterized as basal and luminal epithelial cells by immunostaining for cytokeratin 5 and cytokeratin 8, respectively [23].

Analytical, diagnostic and therapeutic context of Krt2-8

• The amounts of corresponding transcripts were compared; cytokeratin 8 and 18 mRNAs were present at similar levels in hepatocytes freshly isolated from adult liver and, unexpectedly, from 17-day-old foetuses and newborn rats, whereas they were markedly higher in regenerating hepatocytes isolated early after partial hepatectomy [24].
• Activation of plasminogen bound to immobilized CK 8 was accelerated compared with plasminogen in solution, as determined using a coupled-substrate fluorescence assay and SDS/PAGE [2].
• Immunoblotting revealed an overall decrease in cytokeratin content, except for CK 8 [3].

References