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. 1982 Oct 1;95(1):285–295. doi: 10.1083/jcb.95.1.285

Different keratin polypeptides in epidermis and other epithelia of human skin: a specific cytokeratin of molecular weight 46,000 in epithelia of the pilosebaceous tract and basal cell epitheliomas

PMCID: PMC2112346  PMID: 6183270

Abstract

Cytokeratin polypeptides of human epidermis, of epithelia microdissected from various zones of the pilosebaceous tract (outer root-sheath of hair follicle, sebaceous gland), and of eccrine sweat- glands have been separated by one- and two-dimensional gel electrophoresis and characterized by binding of cytokeratin antibodies and by peptide mapping. The epithelium of the pilosebaceous tract has three major keratin polypeptides in common with interfollicular epidermis (two basic components of mol wts 58,000 and 56,000 and one acidic polypeptide of mol wt 50,000); however, it lacks basic keratin polypeptides in the mol wt range of 64,000-68,000 and two acidic keratin-polypeptides of mol wts 56,000 and 56,500 and contains an additional characteristic acidic cytokeratin of mol wt 46,000. Another cytokeratin polypeptide of mol wt 48,000 that is prominent in hair- follicle epithelium is also found in nonfollicular epidermis of foot sole. Both epidermis and pilosebaceous tract are different from eccrine sweat-gland epithelium, which also contains two major cytokeratins of mol wts 52,500 and 54,000 (isoelectric at pH 5.8-6.1) and a more acidic cytokeratin of mol wt 40,000. A striking similarity between the cytokeratins of human basal-cell epitheliomas and those of the pilosebaceous tract has been found: all three major cytokeratins (mol wts 58,000; 50,000; 46,000) of the tumor cells are also expressed in hair-follicle epithelium. The cytokeratin of mol wt 46,000, which is the most prominent acidic cytokeratin in this tumor, is related, by immunological and peptide map criteria, to the acidic keratin- polypeptides of mol wts 48,000 and 50,000, but represents a distinct keratin that is also found in other human tumor cells such as in solid adamantinomas and in cultured HeLa cells. The results show that the various epithelia present in skin, albeit in physical and ontogenic continuity, can be distinguished by their specific cytokeratin- polypeptide patterns and that the cytoskeleton of basal-cell epitheliomas is related to that of cells of the pilosebaceous tract.

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Selected References

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  1. Baden H. P., Lee L. D. Fibrous protein of human epidermis. J Invest Dermatol. 1978 Aug;71(2):148–151. doi: 10.1111/1523-1747.ep12546905. [DOI] [PubMed] [Google Scholar]
  2. Banks-Schlegel S. P., Schlegel R., Pinkus G. S. Keratin protein domains within the human epidermis. Exp Cell Res. 1981 Dec;136(2):465–469. doi: 10.1016/0014-4827(81)90028-8. [DOI] [PubMed] [Google Scholar]
  3. Bowden P. E., Cunliffe W. J. Modification of human prekeratin during epidermal differentiation. Biochem J. 1981 Oct 1;199(1):145–154. doi: 10.1042/bj1990145. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bruder G., Heid H., Jarasch E. D., Keenan T. W., Mather I. H. Characteristics of membrane-bound and soluble forms of xanthine oxidase from milk and endothelial cells of capillaries. Biochim Biophys Acta. 1982 Mar 4;701(3):357–369. doi: 10.1016/0167-4838(82)90239-4. [DOI] [PubMed] [Google Scholar]
  5. Denk H., Krepler R., Lackinger E., Artlieb U., Franke W. W. Biochemical and immunocytochemical analysis of the intermediate filament cytoskeleton in human hepatocellular carcinomas and in hepatic neoplastic nodules of mice. Lab Invest. 1982 Jun;46(6):584–596. [PubMed] [Google Scholar]
  6. Doran T. I., Vidrich A., Sun T. T. Intrinsic and extrinsic regulation of the differentiation of skin, corneal and esophageal epithelial cells. Cell. 1980 Nov;22(1 Pt 1):17–25. doi: 10.1016/0092-8674(80)90150-6. [DOI] [PubMed] [Google Scholar]
  7. Drochmans P., Freudenstein C., Wanson J. C., Laurent L., Keenan T. W., Stadler J., Leloup R., Franke W. W. Structure and biochemical composition of desmosomes and tonofilaments isolated from calf muzzle epidermis. J Cell Biol. 1978 Nov;79(2 Pt 1):427–443. doi: 10.1083/jcb.79.2.427. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Elder J. H., Pickett R. A., 2nd, Hampton J., Lerner R. A. Radioiodination of proteins in single polyacrylamide gel slices. Tryptic peptide analysis of all the major members of complex multicomponent systems using microgram quantities of total protein. J Biol Chem. 1977 Sep 25;252(18):6510–6515. [PubMed] [Google Scholar]
  9. Franke W. W., Appelhans B., Schmid E., Freudenstein C., Osborn M., Weber K. Identification and characterization of epithelial cells in mammalian tissues by immunofluorescence microscopy using antibodies to prekeratin. Differentiation. 1979;15(1):7–25. doi: 10.1111/j.1432-0436.1979.tb01030.x. [DOI] [PubMed] [Google Scholar]
  10. Franke W. W., Denk H., Kalt R., Schmid E. Biochemical and immunological identification of cytokeratin proteins present in hepatocytes of mammalian liver tissue. Exp Cell Res. 1981 Feb;131(2):299–318. doi: 10.1016/0014-4827(81)90234-2. [DOI] [PubMed] [Google Scholar]
  11. Franke W. W., Mayer D., Schmid E., Denk H., Borenfreund E. Differences of expression of cytoskeletal proteins in cultured rat hepatocytes and hepatoma cells. Exp Cell Res. 1981 Aug;134(2):345–365. doi: 10.1016/0014-4827(81)90435-3. [DOI] [PubMed] [Google Scholar]
  12. Franke W. W., Schiller D. L., Moll R., Winter S., Schmid E., Engelbrecht I., Denk H., Krepler R., Platzer B. Diversity of cytokeratins. Differentiation specific expression of cytokeratin polypeptides in epithelial cells and tissues. J Mol Biol. 1981 Dec 25;153(4):933–959. doi: 10.1016/0022-2836(81)90460-5. [DOI] [PubMed] [Google Scholar]
  13. Franke W. W., Schmid E., Breitkreutz D., Lüder M., Boukamp P., Fusenig N. E., Osborn M., Weber K. Simultaneous expression of two different types of intermediate sized filaments in mouse keratinocytes proliferating in vitro. Differentiation. 1979;14(1-2):35–50. doi: 10.1111/j.1432-0436.1979.tb01010.x. [DOI] [PubMed] [Google Scholar]
  14. Franke W. W., Schmid E., Freudenstein C., Appelhans B., Osborn M., Weber K., Keenan T. W. Intermediate-sized filaments of the prekeratin type in myoepithelial cells. J Cell Biol. 1980 Mar;84(3):633–654. doi: 10.1083/jcb.84.3.633. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Franke W. W., Schmid E., Osborn M., Weber K. Different intermediate-sized filaments distinguished by immunofluorescence microscopy. Proc Natl Acad Sci U S A. 1978 Oct;75(10):5034–5038. doi: 10.1073/pnas.75.10.5034. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Franke W. W., Schmid E., Schiller D. L., Winter S., Jarasch E. D., Moll R., Denk H., Jackson B. W., Illmensee K. Differentiation-related patterns of expression of proteins of intermediate-size filaments in tissues and cultured cells. Cold Spring Harb Symp Quant Biol. 1982;46(Pt 1):431–453. doi: 10.1101/sqb.1982.046.01.041. [DOI] [PubMed] [Google Scholar]
  17. Franke W. W., Schmid E., Weber K., Osborn M. HeLa cells contain intermediate-sized filaments of the prekeratin type. Exp Cell Res. 1979 Jan;118(1):95–109. doi: 10.1016/0014-4827(79)90587-1. [DOI] [PubMed] [Google Scholar]
  18. Franke W. W., Weber K., Osborn M., Schmid E., Freudenstein C. Antibody to prekeratin. Decoration of tonofilament like arrays in various cells of epithelial character. Exp Cell Res. 1978 Oct 15;116(2):429–445. doi: 10.1016/0014-4827(78)90466-4. [DOI] [PubMed] [Google Scholar]
  19. Franke W. W., Winter S., Grund C., Schmid E., Schiller D. L., Jarasch E. D. Isolation and characterization of desmosome-associated tonofilaments from rat intestinal brush border. J Cell Biol. 1981 Jul;90(1):116–127. doi: 10.1083/jcb.90.1.116. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Fuchs E. V., Coppock S. M., Green H., Cleveland D. W. Two distinct classes of keratin genes and their evolutionary significance. Cell. 1981 Nov;27(1 Pt 2):75–84. doi: 10.1016/0092-8674(81)90362-7. [DOI] [PubMed] [Google Scholar]
  21. Fuchs E., Green H. Changes in keratin gene expression during terminal differentiation of the keratinocyte. Cell. 1980 Apr;19(4):1033–1042. doi: 10.1016/0092-8674(80)90094-x. [DOI] [PubMed] [Google Scholar]
  22. Fuchs E., Green H. Multiple keratins of cultured human epidermal cells are translated from different mRNA molecules. Cell. 1979 Jul;17(3):573–582. doi: 10.1016/0092-8674(79)90265-4. [DOI] [PubMed] [Google Scholar]
  23. Fuchs E., Green H. Regulation of terminal differentiation of cultured human keratinocytes by vitamin A. Cell. 1981 Sep;25(3):617–625. doi: 10.1016/0092-8674(81)90169-0. [DOI] [PubMed] [Google Scholar]
  24. Fuchs E., Green H. The expression of keratin genes in epidermis and cultured epidermal cells. Cell. 1978 Nov;15(3):887–897. doi: 10.1016/0092-8674(78)90273-8. [DOI] [PubMed] [Google Scholar]
  25. Gabbiani G., Kapanci Y., Barazzone P., Franke W. W. Immunochemical identification of intermediate-sized filaments in human neoplastic cells. A diagnostic aid for the surgical pathologist. Am J Pathol. 1981 Sep;104(3):206–216. [PMC free article] [PubMed] [Google Scholar]
  26. Gilmartin M. E., Culbertson V. B., Freedberg I. M. Phosphorylation of epidermal keratins. J Invest Dermatol. 1980 Sep;75(3):211–216. doi: 10.1111/1523-1747.ep12522887. [DOI] [PubMed] [Google Scholar]
  27. Golitz L. E., Norris D. A., Luekens C. A., Jr, Charles D. M. Nevoid basal cell carcinoma syndrome. Multiple basal cell carcinomas of the palms after radiation therapy. Arch Dermatol. 1980 Oct;116(10):1159–1163. doi: 10.1001/archderm.116.10.1159. [DOI] [PubMed] [Google Scholar]
  28. Green H. The keratinocyte as differentiated cell type. Harvey Lect. 1980;74:101–139. [PubMed] [Google Scholar]
  29. Jackson B. W., Grund C., Schmid E., Bürki K., Franke W. W., Illmensee K. Formation of cytoskeletal elements during mouse embryogenesis. Intermediate filaments of the cytokeratin type and desmosomes in preimplantation embryos. Differentiation. 1980;17(3):161–179. doi: 10.1111/j.1432-0436.1980.tb01093.x. [DOI] [PubMed] [Google Scholar]
  30. Jones H. W., Jr, McKusick V. A., Harper P. S., Wuu K. D. George Otto Gey. (1899-1970). The HeLa cell and a reappraisal of its origin. Obstet Gynecol. 1971 Dec;38(6):945–949. [PubMed] [Google Scholar]
  31. Kubilus J., Baden H. P., McGilvray N. Filamentous protein of basal cell epithelioma: characteristics in vivo and in vitro. J Natl Cancer Inst. 1980 Nov;65(5):869–875. [PubMed] [Google Scholar]
  32. Lee L. D., Baden H. P. Organisation of the polypeptide chains in mammalian keratin. Nature. 1976 Nov 25;264(5584):377–379. doi: 10.1038/264377a0. [DOI] [PubMed] [Google Scholar]
  33. Lee L. D., Kubilus J., Baden H. P. Intraspecies heterogeneity of epidermal keratins isolated from bovine hoof and snout. Biochem J. 1979 Jan 1;177(1):187–196. doi: 10.1042/bj1770187. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Lesot H., Meyer J. M., Ruch J. V., Weber K., Osborn M. Immunofluorescent localization of vimentin, prekeratin and actin during odontoblast and ameloblast differentiation. Differentiation. 1982;21(2):133–137. doi: 10.1111/j.1432-0436.1982.tb01206.x. [DOI] [PubMed] [Google Scholar]
  35. Lonsdale-Eccles J. D., Lynley A. M., Dale B. A. Cyanogen bromide cleavage of proteins in sodium dodecyl sulphate/polyacrylamide gels. Diagonal peptide mapping of proteins from epidermis. Biochem J. 1981 Sep 1;197(3):591–597. doi: 10.1042/bj1970591. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Milstone L. M., McGuire J. Different polypeptides form the intermediate filaments in bovine hoof and esophageal epithelium and in aortic endothelium. J Cell Biol. 1981 Feb;88(2):312–316. doi: 10.1083/jcb.88.2.312. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Renner W., Franke W. W., Schmid E., Geisler N., Weber K., Mandelkow E. Reconstitution of intermediate-sized filaments from denatured monomeric vimentin. J Mol Biol. 1981 Jun 25;149(2):285–306. doi: 10.1016/0022-2836(81)90303-x. [DOI] [PubMed] [Google Scholar]
  38. Schlegel R., Banks-Schlegel S., McLeod J. A., Pinkus G. S. Immunoperoxidase localization of keratin in human neoplasms: a preliminary survey. Am J Pathol. 1980 Oct;101(1):41–49. [PMC free article] [PubMed] [Google Scholar]
  39. Steinert P. M., Idler W. W. The polypeptide composition of bovine epidermal alpha-keratin. Biochem J. 1975 Dec;151(3):603–614. doi: 10.1042/bj1510603. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Steinert P. M., Idler W. W., Wantz M. L. Characterization of the keratin filament subunits unique to bovine snout epidermis. Biochem J. 1980 Jun 1;187(3):913–916. doi: 10.1042/bj1870913. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Steinert P. M., Idler W. W., Zimmerman S. B. Self-assembly of bovine epidermal keratin filaments in vitro. J Mol Biol. 1976 Dec 15;108(3):547–567. doi: 10.1016/s0022-2836(76)80136-2. [DOI] [PubMed] [Google Scholar]
  42. Steinert P. M., Wantz M. L., Idler W. W. O-phosphoserine content of intermediate filament subunits. Biochemistry. 1982 Jan 5;21(1):177–183. doi: 10.1021/bi00530a030. [DOI] [PubMed] [Google Scholar]
  43. Steinert P., Yuspa S. H. Biochemical evidence for keratinization by mouse epidermal cells in culture. Science. 1978 Jun 30;200(4349):1491–1493. doi: 10.1126/science.566466. [DOI] [PubMed] [Google Scholar]
  44. Sun T. T., Green H. Immunofluorescent staining of keratin fibers in cultured cells. Cell. 1978 Jul;14(3):469–476. doi: 10.1016/0092-8674(78)90233-7. [DOI] [PubMed] [Google Scholar]
  45. Sun T. T., Green H. Keratin filaments of cultured human epidermal cells. Formation of intermolecular disulfide bonds during terminal differentiation. J Biol Chem. 1978 Mar 25;253(6):2053–2060. [PubMed] [Google Scholar]
  46. Switzer R. C., 3rd, Merril C. R., Shifrin S. A highly sensitive silver stain for detecting proteins and peptides in polyacrylamide gels. Anal Biochem. 1979 Sep 15;98(1):231–237. doi: 10.1016/0003-2697(79)90732-2. [DOI] [PubMed] [Google Scholar]
  47. Tezuka T., Freedberg I. M. Epidermal structural proteins. II. Isolation and purification of tonofilaments of the newborn rat. Biochim Biophys Acta. 1972 Apr 15;263(2):382–396. [PubMed] [Google Scholar]
  48. Thomas J. O., Kornberg R. D. An octamer of histones in chromatin and free in solution. Proc Natl Acad Sci U S A. 1975 Jul;72(7):2626–2630. doi: 10.1073/pnas.72.7.2626. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Towbin H., Staehelin T., Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. doi: 10.1073/pnas.76.9.4350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Winter H., Schweizer J., Goerttler K. Keratins as markers of malignancy in mouse epidermal tumors. Carcinogenesis. 1980 May;1(5):391–398. doi: 10.1093/carcin/1.5.391. [DOI] [PubMed] [Google Scholar]
  51. Wu Y. J., Rheinwald J. G. A new small (40 kd) keratin filament protein made by some cultured human squamous cell carcinomas. Cell. 1981 Sep;25(3):627–635. doi: 10.1016/0092-8674(81)90170-7. [DOI] [PubMed] [Google Scholar]

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