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Gene Review

Krt8  -  keratin 8, type II

Rattus norvegicus

Synonyms: CK-8, CYKER, Cytokeratin endo A, Cytokeratin-8, K8, ...
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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


Biological context of Krt2-8


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].


  1. Contrasting effects of K8 and K18 on stabilizing K19 expression, cell motility and tumorigenicity in the BSp73 adenocarcinoma. Pankov, R., Simcha, I., Zöller, M., Oshima, R.G., Ben-Ze'ev, A. J. Cell. Sci. (1997) [Pubmed]
  2. Cytokeratin 8 released by breast carcinoma cells in vitro binds plasminogen and tissue-type plasminogen activator and promotes plasminogen activation. Hembrough, T.A., Kralovich, K.R., Li, L., Gonias, S.L. Biochem. J. (1996) [Pubmed]
  3. Liarozole, an antitumor drug, modulates cytokeratin expression in the Dunning AT-6sq prostatic carcinoma through in situ accumulation of all-trans-retinoic acid. Smets, G., Van Ginckel, R., Daneels, G., Moeremans, M., Van Wauwe, J., Coene, M.C., Ramaekers, F.C., Schalken, J.A., Borgers, M., De Coster, R. Prostate (1995) [Pubmed]
  4. Down-regulation of cytokeratin 14 gene expression by the polyoma virus middle T antigen is dependent on c-Src association but independent of full transformation in rat liver nonparenchymal epithelial cells. Royal, I., Raptis, L., Druker, B.J., Marceau, N. Cell Growth Differ. (1996) [Pubmed]
  5. Reconstruction of hepatic organoid by rat small hepatocytes and hepatic nonparenchymal cells. Mitaka, T., Sato, F., Mizuguchi, T., Yokono, T., Mochizuki, Y. Hepatology (1999) [Pubmed]
  6. Generation of hepatocytes from oval cell precursors in culture. Lázaro, C.A., Rhim, J.A., Yamada, Y., Fausto, N. Cancer Res. (1998) [Pubmed]
  7. Exposure of primary rat hepatocytes in long-term DMSO culture to selected transition metals induces hepatocyte proliferation and formation of duct-like structures. Cable, E.E., Isom, H.C. Hepatology (1997) [Pubmed]
  8. Ductular hepatocytes. Evidence for a bile ductular cell origin in furan-treated rats. Sirica, A.E., Gainey, T.W., Mumaw, V.R. Am. J. Pathol. (1994) [Pubmed]
  9. Arginine induced acute pancreatitis alters the actin cytoskeleton and increases heat shock protein expression in rat pancreatic acinar cells. Tashiro, M., Schäfer, C., Yao, H., Ernst, S.A., Williams, J.A. Gut (2001) [Pubmed]
  10. Keratin 8 phosphorylation in vitro by cAMP-dependent protein kinase occurs within the amino- and carboxyl-terminal end domains. Ando, S., Tokui, T., Yano, T., Inagaki, M. Biochem. Biophys. Res. Commun. (1996) [Pubmed]
  11. Polyomavirus middle T selective action on cytokeratin 14 gene expression in liver nonparenchymal epithelial cells. Royal, I., Grenier, A., Mailhot, D., Marceau, N. Exp. Cell Res. (1995) [Pubmed]
  12. Desmin expressing nonhematopoietic liver cells during rat liver development: an immunohistochemical and morphometric study. Kiassov, A.P., Van Eyken, P., van Pelt, J.F., Depla, E., Fevery, J., Desmet, V.J., Yap, S.H. Differentiation (1995) [Pubmed]
  13. Androgen repression of cytokeratin gene expression during rat prostate differentiation: evidence for an epithelial stem cell-associated marker. Wang, X., Hsieh, J.T. Chin. Med. Sci. J. (1994) [Pubmed]
  14. Differential expression of acidic cytokeratins 18 and 19 during sexual differentiation of the rat gonad. Fridmacher, V., Locquet, O., Magre, S. Development (1992) [Pubmed]
  15. Cytokeratin expression patterns in the rat respiratory tract as markers of epithelial differentiation in inhalation toxicology. II. Changes in cytokeratin expression patterns following 8-day exposure to room-aged cigarette sidestream smoke. Schlage, W.K., Bülles, H., Friedrichs, D., Kuhn, M., Teredesai, A., Terpstra, P.M. Toxicologic pathology. (1998) [Pubmed]
  16. Heterogeneity of rat thymic epithelium defined by monoclonal anti-keratin antibodies. Colić, M., Matanović, D., Hegedis, L., Dujić, A. Thymus (1988) [Pubmed]
  17. Heterogeneity in the immunolocalization of cytokeratin specific monoclonal antibodies in the rat eye: evaluation of unusual epithelial tissue entities. Kasper, M. Histochemistry (1991) [Pubmed]
  18. The resistant hepatocyte model of carcinogenesis in the rat: the apparent independent development of oval cell proliferation and early nodules. Anilkumar, T.V., Golding, M., Edwards, R.J., Lalani, E.N., Sarraf, C.E., Alison, M.R. Carcinogenesis (1995) [Pubmed]
  19. Protein phosphatases maintain the organization and structural interactions of hepatic keratin intermediate filaments. Toivola, D.M., Goldman, R.D., Garrod, D.R., Eriksson, J.E. J. Cell. Sci. (1997) [Pubmed]
  20. Developmental exposure to estrogens alters epithelial cell adhesion and gap junction proteins in the adult rat prostate. Habermann, H., Chang, W.Y., Birch, L., Mehta, P., Prins, G.S. Endocrinology (2001) [Pubmed]
  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. Pisters, L.L., Wang, X.H., Chung, L.W., Hsieh, J.T. Prostate (2001) [Pubmed]
  22. Effects of mitogens and co-mitogens on the formation of small-cell colonies in primary cultures of rat hepatocytes. Mitaka, T., Norioka, K., Nakamura, T., Mochizuki, Y. J. Cell. Physiol. (1993) [Pubmed]
  23. Isolation of rat ventral prostate basal and luminal epithelial cells by the STAPUT technique. Ravindranath, N., Dym, M. Prostate (1999) [Pubmed]
  24. Distinct effects of cell-cell communication and corticosteroids on the synthesis and distribution of cytokeratins in cultured rat hepatocytes. Baffet, G., Loyer, P., Glaise, D., Corlu, A., Etienne, P.L., Guguen-Guillouzo, C. J. Cell. Sci. (1991) [Pubmed]
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