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Changes in keratin expression during malignant progression of transformed mouse epidermal keratinocytes.
- Source :
-
Experimental cell research [Exp Cell Res] 1993 Jan; Vol. 204 (1), pp. 11-21. - Publication Year :
- 1993
-
Abstract
- We have studied in this report the expression of keratins in mouse epidermal keratinocytes transformed in culture by a chemical carcinogen (PDV) and in cell lines (PDVCM1, PDVCM2, PDVCV1, and PDVC57) derived by tumor transplantation of PDV cells in syngeneic C57Bl/6 mice. PDV, PDVCM1, PDVCM2, and PDVCV1 cell lines are weakly to moderately tumorigenic, giving rise to squamous cell carcinomas, although not at all injection points, whereas PDVC57 cells are more malignant, inducing highly anaplastic carcinomas at 100% of injection sites. All the cell lines synthesize anomalously simple epithelial keratins, substantial amounts of K8, and minor quantities of K18 and K19, but the level of expression is increased in PDVC57. We have found that in PDVC57 cells upregulation of K8 is linked to down-regulation of the normal keratins produced by epidermal keratinocytes in culture (i.e., K5, K6, K14, and K17). On the other hand, K8 does not generally colocalize with K13, a keratin also aberrantly expressed by epidermal cell cultures when induced to differentiate by high Ca2+ medium. K13, normally synthesized in internal stratified epithelia, is anomalously induced in mouse epidermal tumors and has been used as an early marker of carcinoma progression. In tumors induced by the cell lines upon injection in mice, K8 is found in the less differentiated regions as opposite to K13, restricted to the differentiating areas of the tumors. In PDV, PDVCM1, PDVCM2, and PDVCV1 carcinomas the overall expression of K13 is higher than that of K8. However, this relation is inverted in tumors induced by PDVC57 cells, in a good correlation with the tumoral phenotypes produced by the cell lines. Our results suggest that upregulation of the simple epithelial keratin K8, as found in transformed epidermal cell lines and tumors, is a late marker of malignant progression and is associated with the loss of the differentiated phenotype.
- Subjects :
- 9,10-Dimethyl-1,2-benzanthracene
Animals
Carcinoma etiology
Carcinoma metabolism
Carcinoma, Squamous Cell etiology
Carcinoma, Squamous Cell metabolism
Cell Line, Transformed
Genes, ras
Keratinocytes pathology
Mice
Mice, Inbred C57BL
Neoplasm Transplantation
Skin Neoplasms etiology
Skin Neoplasms metabolism
Skin Neoplasms pathology
Up-Regulation
Carcinoma pathology
Carcinoma, Squamous Cell pathology
Cell Transformation, Neoplastic
Keratinocytes metabolism
Keratins biosynthesis
Subjects
Details
- Language :
- English
- ISSN :
- 0014-4827
- Volume :
- 204
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Experimental cell research
- Publication Type :
- Academic Journal
- Accession number :
- 7677983
- Full Text :
- https://doi.org/10.1006/excr.1993.1003