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Localization of a M_r 52,000 Keratin in Basal Epith Mouse Bladder and Expression throughout Neoplastic Progression¹

Sidney Farber Cancer Institute, Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115

In this study, we report the isolation of a M_r 52,000 keratin from a nontumorigenic bladder epithelial cell line and its localization, by immunofluorescence, in bladder frozen sections at different stages of neoplastic progression and in various carcinogen-transformed bladder epithelial cells and human bladder carcinoma-derived cell lines. The results showed that: (a) the M, 52,000 keratin is present in basal epithelial cells of the normal bladder but absent from the intermediate and superficial epithelial cell layers; (b) hyperplastic bladder lesions, induced in mice after the administration of butyl-(4-hydroxybutyl)-nitrosamine, resulted primarily from th eproliferation of cells in the basal compartment; (c) butyl-(4-hydroxybutyl)nitrosamine-induced bladder carcinomas displayed differential staining with the anti-M, 52,000 keratin antiserum reflecting divergent differentiated status within a tumor and a subpopulation of cells with reduced overall keratin expression; (d) primary cultures of bladder carcinomas revealed a subpopulation of cells with limited filamentous keratin as was observed in vivo; (e) mouse bladder epithelial cell lines transformed in culture by a chemical carcinogen showed a loss or reduction in expression of the M_r 52,000 keratin; (f) two human bladder carcinoma cell lines displayed very limited expression of the M_r 52,000 keratin. Although the loss or reduction in expression of a specific keratin in unlikely to be responsible for transformation, it may contribute to the heterogeneity in the differentiated state and morphology of bladder epithelial cells during neoplastic progression both in vivo and in culture.

¹ Supported by NIH Grant CA-29793.

² Recipient of American Cancer Society Faculty Research Award. To whom requests for reprints should be addressed, at the Sidney Farber Cancer Institute, 44 Binney Street, Boston, Mass. 02115.

Received 1/ 7/82. Accepted 7/ 1/82.

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