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.
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Selected References
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- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]