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Changes in Regional Keratin Polypeptide Patterns during Phorbol Estermediated Reversible and Permanently Sustained Hyperplasia of Mouse Epidermis¹

German Cancer Research Center, Institute of Experimental Pathology, Im Neuenheimer Feld 280, 6900 Heidelberg, Federal Republic of Germany

The keratin polypeptide pattern of newborn mouse back, ear, and tail epidermis is uniform and consists of eight individual proteins with a molecular weight range of 46,000 to 67,000. In the adult animal, the keratin patterns of the corresponding body sites are both different from the neonatal pattern and different among themselves. Most notably, ear and tail epidermis contains a high-molecular-weight polypeptide (M_r, 70,000), which is absent from neonatal and adult back epidermis. This postnatal specialization of the local program of keratin polypeptide synthesis cannot be related to distinct morphological criteria.

We have analyzed the behavior of these regional keratinization phenotypes in the adult mouse under the influence of a reversible or a permanently sustained hyperplasia. Both types of epidermal trauma were induced by either single or repeated treatment of skin with tumor-promoting or nonpromoting hyperplasiogens. Independent of the type of hyperplasiogen used, the initial phase of a reversible hyperplasia (0 to 12 hr) is characterized by only marginal morphological alterations, maintenance of the normal one-dimensional keratin pattern, but pronounced changes in the charge properties of distinct keratin polypeptides, indicating disturbances of the secondary phosphorylation-dephosphorylation process. During the acute phase of reversible hyperplasia (1 to 7 days), the local keratinization phenotypes are quantitatively altered due to the enhanced expression of high-molecular-weight keratin polypeptides. However, the charge properties of the newly synthesized proteins appear normal. A comparison of both the sequential morphological alterations during acute hyperplasia and the temporally corresponding changes in the keratin patterns allows an assignment of the site of synthesis of distinct polypeptides within the epidermis, which is in line with findings of other laboratories. Long-term hyperplasia (2 weeks to 2 months of regular treatment) is not morphologically different from maximum reversible hyperplasia. However, it induces both quantitative and qualitative alterations of the local keratinization phenotypes and causes a reversal of the postnatal divergence of keratin synthesis by generally restoring the neonatal keratin pattern in all three adult epithelia investigated.

¹ Parts of this investigation have been presented at the symposium, "Cocarcinogenesis and Biological Effects of Tumor Promoters", October 13 to 16, 1980, Castle of Elmau, Federal Republic of Germany.

Received 7/31/81. Accepted 12/15/81.

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