Keratin 8

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Keratin, type II cytoskeletal 8 also known as cytokeratin-8 (CK-8) or keratin-8 (K8) is a keratin protein that is encoded in humans by the KRT8 gene. It is often paired with keratin 18.

Utility as an immunohistochemical stain

Antibodies to CK8 (e.g. CAM 5.2) can be used to differentiate lobular carcinoma of the breast from ductal carcinoma of the breast.[1] CAM 5.2, an antibody that reacts with an epitope found on both CK8 and CK18, is used in immunohistochemistry to demonstrate certain forms of cancer. In normal tissue, it reacts mainly with secretory epithelia, but not with squamous epithelium, such as that found in the skin, cervix, and esophagus. However, it also reacts with a range of malignant cells, including those derived from secretory epithelia, but also some squamous carcinomata, such as spindle cell carcinoma. It is considered useful in identifying microscopic metastases of breast carcinoma in lymph nodes, and in distinguishing Paget's disease from malignant melanoma. It also reacts with neuroendocrine tumors.[2]

Keratin 8 is often used together with keratin 18 and keratin 19 to differentiate cells of epithelial origin from hematopoietic cells in tests that enumerate circulating tumor cells in blood.[3]

Interactions

Keratin 8 has been shown to interact with MAPK14,[4] Pinin[5] and PPL.[6]

File:Cytokeratin 8.jpg
Cytokeratin 8 staining in the human breast cancer cell line MCF-7

See also


References

  1. Moriya T, Kasajima A, Ishida K, et al. (March 2006). "New trends of immunohistochemistry for making differential diagnosis of breast lesions". Med Mol Morphol. 39 (1): 8–13. doi:10.1007/s00795-006-0309-8. PMID 16575508.
  2. Leong, Anthony S-Y; Cooper, Kumarason; Leong, F Joel W-M (2003). Manual of Diagnostic Cytology (2 ed.). Greenwich Medical Media, Ltd. pp. 177–178. ISBN 1-84110-100-1.
  3. W. Jeffrey Allard; Jeri Matera; M. Craig Miller; et al. (October 2004). "Tumor Cells Circulate in the Peripheral Blood of All Major Carcinomas but not in Healthy Subjects or Patients With Nonmalignant Diseases". Clin. Cancer Research. 10 (20): 6897–6904. doi:10.1158/1078-0432.CCR-04-0378. PMID 15501967.
  4. Ku, Nam-On; Azhar Salman; Omary M Bishr (March 2002). "Keratin 8 phosphorylation by p38 kinase regulates cellular keratin filament reorganization: modulation by a keratin 1-like disease causing mutation". J. Biol. Chem. United States. 277 (13): 10775–82. doi:10.1074/jbc.M107623200. ISSN 0021-9258. PMID 11788583.
  5. Shi, J; Sugrue S P (May 2000). "Dissection of protein linkage between keratins and pinin, a protein with dual location at desmosome-intermediate filament complex and in the nucleus". J. Biol. Chem. UNITED STATES. 275 (20): 14910–5. doi:10.1074/jbc.275.20.14910. ISSN 0021-9258. PMID 10809736.
  6. Kazerounian, Shideh; Uitto Jouni; Aho Sirpa (October 2002). "Unique role for the periplakin tail in intermediate filament association: specific binding to keratin 8 and vimentin". Exp. Dermatol. Denmark. 11 (5): 428–38. doi:10.1034/j.1600-0625.2002.110506.x. ISSN 0906-6705. PMID 12366696.

Further reading

  • Moll R, Franke WW, Schiller DL, et al. (1983). "The catalog of human cytokeratins: patterns of expression in normal epithelia, tumors and cultured cells". Cell. 31 (1): 11–24. doi:10.1016/0092-8674(82)90400-7. PMID 6186379.
  • Ljubimov AV, Bartek J, Couchman JR, et al. (1992). "Distribution of individual components of basement membrane in human colon polyps and adenocarcinomas as revealed by monoclonal antibodies". Int. J. Cancer. 50 (4): 562–6. doi:10.1002/ijc.2910500412. PMID 1371500.
  • Smedts F, Ramaekers F, Robben H, et al. (1990). "Changing patterns of keratin expression during progression of cervical intraepithelial neoplasia". Am. J. Pathol. 136 (3): 657–68. PMC 1877502. PMID 1690513.
  • Krauss S, Franke WW (1990). "Organization and sequence of the human gene encoding cytokeratin 8". Gene. 86 (2): 241–9. doi:10.1016/0378-1119(90)90285-Y. PMID 1691124.
  • Yamamoto R, Kao LC, McKnight CE, Strauss JF (1990). "Cloning and sequence of cDNA for human placental cytokeratin 8. Regulation of the mRNA in trophoblastic cells by cAMP". Mol. Endocrinol. 4 (3): 370–4. doi:10.1210/mend-4-3-370. PMID 1692965.
  • Waseem A, Alexander CM, Steel JB, Lane EB (1991). "Embryonic simple epithelial keratins 8 and 18: chromosomal location emphasizes difference from other keratin pairs". New Biol. 2 (5): 464–78. PMID 1705144.
  • Tsubura A, Okada H, Sasaki M, et al. (1991). "Immunohistochemical demonstration of keratins 8 and 14 in benign tumours of the skin appendage". Virchows Archiv A. 418 (6): 503–7. doi:10.1007/BF01606500. PMID 1711732.
  • Leube RE, Bosch FX, Romano V, et al. (1987). "Cytokeratin expression in simple epithelia. III. Detection of mRNAs encoding human cytokeratins nos. 8 and 18 in normal and tumor cells by hybridization with cDNA sequences in vitro and in situ". Differentiation. 33 (1): 69–85. doi:10.1111/j.1432-0436.1986.tb00412.x. PMID 2434381.
  • Guelstein VI, Tchypysheva TA, Ermilova VD, et al. (1988). "Monoclonal antibody mapping of keratins 8 and 17 and of vimentin in normal human mammary gland, benign tumors, dysplasias and breast cancer". Int. J. Cancer. 42 (2): 147–53. doi:10.1002/ijc.2910420202. PMID 2456993.
  • Osborn M, Mazzoleni G, Santini D, et al. (1988). "Villin, intestinal brush border hydrolases and keratin polypeptides in intestinal metaplasia and gastric cancer; an immunohistologic study emphasizing the different degrees of intestinal and gastric differentiation in signet ring cell carcinomas". Virchows Archiv A. 413 (4): 303–12. doi:10.1007/BF00783022. PMID 2459839.
  • Fisher HP, Doppl W, Osborn M, Altmannsberger M (1989). "Evidence for a hepatocellular lineage in a combined hepatocellular-cholangiocarcinoma of transitional type". Virchows Archiv B. 56 (2): 71–6. doi:10.1007/bf02890004. PMID 2467436.
  • Kulesh DA, Ceceña G, Darmon YM, et al. (1989). "Posttranslational regulation of keratins: degradation of mouse and human keratins 18 and 8". Mol. Cell. Biol. 9 (4): 1553–65. PMC 362572. PMID 2471065.
  • Gel'shteĭn VI, Chipysheva TA, Ermilova VD, Bannikov GA (1990). "[The expression of keratins Nos. 8, 17 and vimentin in pleomorphic adenoma of the salivary glands]". Arkh. Patol. 51 (10): 28–35. PMID 2482017.
  • Eichbaum QG, Beatty DW, Parker MI (1994). "Identification of cardiac autoantigens in human heart cDNA libraries using acute rheumatic fever sera". J. Autoimmun. 7 (2): 243–61. doi:10.1006/jaut.1994.1019. PMID 8037842.
  • Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
  • Ku NO, Omary MB (1997). "Phosphorylation of human keratin 8 in vivo at conserved head domain serine 23 and at epidermal growth factor-stimulated tail domain serine 431". J. Biol. Chem. 272 (11): 7556–64. doi:10.1074/jbc.272.11.7556. PMID 9054461.
  • Ji H, Reid GE, Moritz RL, et al. (1997). "A two-dimensional gel database of human colon carcinoma proteins". Electrophoresis. 18 (3–4): 605–13. doi:10.1002/elps.1150180344. PMID 9150948.
  • Liao J, Ku NO, Omary MB (1997). "Stress, apoptosis, and mitosis induce phosphorylation of human keratin 8 at Ser-73 in tissues and cultured cells". J. Biol. Chem. 272 (28): 17565–73. doi:10.1074/jbc.272.28.17565. PMID 9211903.
  • Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.

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