Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1984 Jul;81(14):4280–4284. doi: 10.1073/pnas.81.14.4280

Differences in keratin synthesis between normal epithelial cells and squamous cell carcinomas are mediated by vitamin A.

K H Kim, F Schwartz, E Fuchs
PMCID: PMC345571  PMID: 6205393

Abstract

A number of recent studies have indicated that the expression of keratins is altered upon malignant transformation of human epithelial cells. We have shown that the altered expression of 67-kDa and 40-kDa keratins in established squamous cell carcinoma lines from tongue and epidermis stems largely from a difference in their sensitivity to vitamin A apparently acquired during tumorigenesis. When the vitamin A concentration in the medium is raised, the 40-kDa keratin is produced at increased levels. Conversely, when the amount of vitamin is reduced, the 67-kDa keratin is synthesized and the cells undergo stratification and terminal differentiation. However, even when vitamin A is quantitatively removed from the medium, the maximal degree of differentiation attained by each squamous cell carcinoma cell as judged by the synthesis of 67-kDa keratin was still less than that of the normal keratinocytes. These findings suggest that the altered patterns of keratins observed for some tissues upon malignant transformation arise from a complex mixture of intracellular changes in the differentiative pathway in addition to changes in the responsiveness of cells to extracellular regulators of keratin gene expression.

Full text

PDF
4280

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bashor M. M., Toft D. O., Chytil F. In vitro binding of retinol to rat-tissue components. Proc Natl Acad Sci U S A. 1973 Dec;70(12):3483–3487. doi: 10.1073/pnas.70.12.3483. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Dale B. A., Stern I. B., Rabin M., Huang L. The identification of fibrous proteins in fetal rat epidermis by electrophoretic and immunologic techniques. J Invest Dermatol. 1976 Apr;66(4):230–235. doi: 10.1111/1523-1747.ep12482148. [DOI] [PubMed] [Google Scholar]
  3. De Ruyter M. G., De Leenheer A. P. Determination of serum retinol (vitamin A) by high-speed liquid chromatography. Clin Chem. 1976 Oct;22(10):1593–1595. [PubMed] [Google Scholar]
  4. Franke W. W., Schiller D. L., Hatzfeld M., Winter S. Protein complexes of intermediate-sized filaments: melting of cytokeratin complexes in urea reveals different polypeptide separation characteristics. Proc Natl Acad Sci U S A. 1983 Dec;80(23):7113–7117. doi: 10.1073/pnas.80.23.7113. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. 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]
  6. 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]
  7. 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]
  8. 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]
  9. Fuchs E., Marchuk D. Type I and type II keratins have evolved from lower eukaryotes to form the epidermal intermediate filaments in mammalian skin. Proc Natl Acad Sci U S A. 1983 Oct;80(19):5857–5861. doi: 10.1073/pnas.80.19.5857. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Green H., Watt F. M. Regulation by vitamin A of envelope cross-linking in cultured keratinocytes derived from different human epithelia. Mol Cell Biol. 1982 Sep;2(9):1115–1117. doi: 10.1128/mcb.2.9.1115. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hanukoglu I., Fuchs E. The cDNA sequence of a Type II cytoskeletal keratin reveals constant and variable structural domains among keratins. Cell. 1983 Jul;33(3):915–924. doi: 10.1016/0092-8674(83)90034-x. [DOI] [PubMed] [Google Scholar]
  12. Hanukoglu I., Fuchs E. The cDNA sequence of a human epidermal keratin: divergence of sequence but conservation of structure among intermediate filament proteins. Cell. 1982 Nov;31(1):243–252. doi: 10.1016/0092-8674(82)90424-x. [DOI] [PubMed] [Google Scholar]
  13. Kim K. H., Rheinwald J. G., Fuchs E. V. Tissue specificity of epithelial keratins: differential expression of mRNAs from two multigene families. Mol Cell Biol. 1983 Apr;3(4):495–502. doi: 10.1128/mcb.3.4.495. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. 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]
  15. Mehta R. G., Kute T. E., Hopkins M., Moon R. C. Retinoic acid binding proteins and steroid receptor levels in human breast cancer. Eur J Cancer Clin Oncol. 1982 Mar;18(3):221–226. doi: 10.1016/0277-5379(82)90040-2. [DOI] [PubMed] [Google Scholar]
  16. Milstone L. M. Isolation and characterization of two polypeptides that form intermediate filaments in bovine esophageal epithelium. J Cell Biol. 1981 Feb;88(2):317–322. doi: 10.1083/jcb.88.2.317. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Moll R., Franke W. W., Schiller D. L., Geiger B., Krepler R. The catalog of human cytokeratins: patterns of expression in normal epithelia, tumors and cultured cells. Cell. 1982 Nov;31(1):11–24. doi: 10.1016/0092-8674(82)90400-7. [DOI] [PubMed] [Google Scholar]
  18. Moll R., Krepler R., Franke W. W. Complex cytokeratin polypeptide patterns observed in certain human carcinomas. Differentiation. 1983;23(3):256–269. doi: 10.1111/j.1432-0436.1982.tb01291.x. [DOI] [PubMed] [Google Scholar]
  19. Rheinwald J. G., Beckett M. A. Defective terminal differentiation in culture as a consistent and selectable character of malignant human keratinocytes. Cell. 1980 Nov;22(2 Pt 2):629–632. doi: 10.1016/0092-8674(80)90373-6. [DOI] [PubMed] [Google Scholar]
  20. Rheinwald J. G., Green H. Serial cultivation of strains of human epidermal keratinocytes: the formation of keratinizing colonies from single cells. Cell. 1975 Nov;6(3):331–343. doi: 10.1016/s0092-8674(75)80001-8. [DOI] [PubMed] [Google Scholar]
  21. Rothblat G. H., Arbogast L. Y., Ouellette L., Howard B. V. Preparation of delipidized serum protein for use in cell culture systems. In Vitro. 1976 Aug;12(8):554–557. doi: 10.1007/BF02797438. [DOI] [PubMed] [Google Scholar]
  22. Schindler J., Matthaei K. I., Sherman M. I. Isolation and characterization of mouse mutant embryonal carcinoma cells which fail to differentiate in response to retinoic acid. Proc Natl Acad Sci U S A. 1981 Feb;78(2):1077–1080. doi: 10.1073/pnas.78.2.1077. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. 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]
  24. Thomas P. S. Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5201–5205. doi: 10.1073/pnas.77.9.5201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Tseng S. C., Jarvinen M. J., Nelson W. G., Huang J. W., Woodcock-Mitchell J., Sun T. T. Correlation of specific keratins with different types of epithelial differentiation: monoclonal antibody studies. Cell. 1982 Sep;30(2):361–372. doi: 10.1016/0092-8674(82)90234-3. [DOI] [PubMed] [Google Scholar]
  26. 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]
  27. Yuspa S. H., Poirier M. C., Harness J. R., Olsom D. R., Steinert P. M. Specific quantification of mouse and human keratin proteins by radioimmunoassay. Biochem J. 1980 Apr 1;187(1):281–284. doi: 10.1042/bj1870281. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES