Subcellular localization of beta-catenin in malignant cell lines and squamous cell carcinomas of the oral cavity.

Abstract

Beta-catenin, an E-cadherin-associated protein involved in cell-cell adhesion and signaling, has been hypothesized to translocate to the nucleus and activate transcription in several human cancers, including oral squamous cell carcinomas (OSCC). In the present study, we analyzed the subcellular localization of beta-catenin in cultures of human oral normal and malignant (cell lines SCC15 and SCC25) keratinocytes and in 24 frozen samples of oral squamous cell carcinomas by a double-staining technique for nucleic acids and beta-catenin. Growth potential, as assessed by cell count at different time periods, was established for normal, SCC15 and SCC25 cell lines; oral squamous cell carcinomas were classified according to the histopathological and malignancy indexes. Beta-catenin localized at the plasma membrane in the normal and SCC15 cells, not in the SCC25 cells, where it localized mostly in the perinuclear and nuclear areas. In the growth assays, SCC25 cell lines proliferated faster than in normal and SCC15 cells over a period of 6 days (cell numbers were significantly different, P < 0.0001). Carcinoma sections showed a combination of membranous, cytoplasmic and, in few invading epithelial islands of two tumors, nuclear localization of beta-catenin. In oral squamous cell carcinomas, nuclear beta-catenin staining was observed only within invading islands of two carcinomas deep in the underlying connective tissue. On the basis of this study, we conclude that intranuclear beta-catenin does not appear to be a common finding in oral squamous cell carcinomas and that a clear association between intranuclear beta-catenin and histopathological and malignancy indexes in vivo could not be established.