Keratin 8 Explained

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]

See also

• Immunohistochemistry

Further reading

• Moll R, Franke WW, Schiller DL, etal . The catalog of human cytokeratins: patterns of expression in normal epithelia, tumors and cultured cells. . Cell . 31 . 1 . 11–24 . 1983 . 6186379 . 10.1016/0092-8674(82)90400-7 . 33701361 .
• Ljubimov AV, Bartek J, Couchman JR, etal . 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 . 1992 . 1371500 . 10.1002/ijc.2910500412 . 40459741 .
• Smedts F, Ramaekers F, Robben H, etal . Changing patterns of keratin expression during progression of cervical intraepithelial neoplasia . Am. J. Pathol. . 136 . 3 . 657–68 . 1990 . 1690513 . 1877502 .
• Krauss S, Franke WW . Organization and sequence of the human gene encoding cytokeratin 8 . Gene . 86 . 2 . 241–9 . 1990 . 1691124 . 10.1016/0378-1119(90)90285-Y .
• Yamamoto R, Kao LC, McKnight CE, Strauss JF . 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 . 1990 . 1692965 . 10.1210/mend-4-3-370 . free .
• Waseem A, Alexander CM, Steel JB, Lane EB . Embryonic simple epithelial keratins 8 and 18: chromosomal location emphasizes difference from other keratin pairs . New Biol. . 2 . 5 . 464–78 . 1991 . 1705144 .
• Tsubura A, Okada H, Sasaki M, etal . Immunohistochemical demonstration of keratins 8 and 14 in benign tumours of the skin appendage . Virchows Archiv A . 418 . 6 . 503–7 . 1991 . 1711732 . 10.1007/BF01606500 . 12052324 .
• Leube RE, Bosch FX, Romano V, etal . 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 . 1987 . 2434381 . 10.1111/j.1432-0436.1986.tb00412.x.
• Guelstein VI, Tchypysheva TA, Ermilova VD, etal . 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 . 1988 . 2456993 . 10.1002/ijc.2910420202 . 30650956 .
• Osborn M, Mazzoleni G, Santini D, etal . 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 . 1988 . 2459839 . 10.1007/BF00783022 . 23830197 .
• Fisher HP, Doppl W, Osborn M, Altmannsberger M . Evidence for a hepatocellular lineage in a combined hepatocellular-cholangiocarcinoma of transitional type . Virchows Archiv B . 56 . 2 . 71–6 . 1989 . 2467436 . 10.1007/bf02890004. 24713975 .
• Kulesh DA, Ceceña G, Darmon YM, etal . Posttranslational regulation of keratins: degradation of mouse and human keratins 18 and 8 . Mol. Cell. Biol. . 9 . 4 . 1553–65 . 1989 . 2471065 . 10.1128/mcb.9.4.1553. 362572 .
• Gel'shteĭn VI, Chipysheva TA, Ermilova VD, Bannikov GA . [The expression of keratins Nos. 8, 17 and vimentin in pleomorphic adenoma of the salivary glands] . Arkh. Patol. . 51 . 10 . 28–35 . 1990 . 2482017 .
• Eichbaum QG, Beatty DW, Parker MI . Identification of cardiac autoantigens in human heart cDNA libraries using acute rheumatic fever sera . J. Autoimmun. . 7 . 2 . 243–61 . 1994 . 8037842 . 10.1006/jaut.1994.1019 .
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–4 . 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Ku NO, Omary MB . 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 . 1997 . 9054461 . 10.1074/jbc.272.11.7556 . free .
• Ji H, Reid GE, Moritz RL, etal . A two-dimensional gel database of human colon carcinoma proteins . Electrophoresis . 18 . 3–4 . 605–13 . 1997 . 9150948 . 10.1002/elps.1150180344 . 25454450 .
• Liao J, Ku NO, Omary MB . 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 . 1997 . 9211903 . 10.1074/jbc.272.28.17565 . free .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, etal . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–56 . 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .

Notes and References

1. Moriya T, Kasajima A, Ishida K, etal . New trends of immunohistochemistry for making differential diagnosis of breast lesions . Med Mol Morphol . 39 . 1 . 8–13 . March 2006 . 16575508 . 10.1007/s00795-006-0309-8 . 5978885 .
2. Book: Leong, Anthony S-Y. Cooper, Kumarason. Leong, F Joel W-M. 2003. Manual of Diagnostic Cytology. 2. Greenwich Medical Media, Ltd.. 177–178. 1-84110-100-1.
3. W. Jeffrey Allard . Jeri Matera . M. Craig Miller . Tumor Cells Circulate in the Peripheral Blood of All Major Carcinomas but not in Healthy Subjects or Patients With Nonmalignant Diseases . Clinical Cancer Research . 10 . 6897–6904 . October 2004 . 10.1158/1078-0432.CCR-04-0378 . 15501967 . 20. etal. free .
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. . 277 . 13 . 10775–82 . United States. 0021-9258. 11788583 . 10.1074/jbc.M107623200 . free .
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. . 275 . 20 . 14910–5 . UNITED STATES. 0021-9258. 10809736 . 10.1074/jbc.275.20.14910 . free .
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. . 11 . 5 . 428–38 . Denmark. 0906-6705. 12366696 . 10.1034/j.1600-0625.2002.110506.x . 25735126 .