Reduced expression and aberrant localization of p120catenin in human squamous cell carcinoma of the skin

Abstract

Background: p120catenin (p120ctn), a member of the Armadillo protein family, is ubiquitously expressed and binds to classical cadherins together with other catenins to participate in the adherens junction. p120ctn has numerous isoforms generated through extensive splicing and alternative usage of translation initiation codons. Although the involvement of p120ctn in cell growth control has been postulated, little has so far been known about its expression patterns in the skin and epidermal tumors. Objective: To identify the isoforms expressed in benign and malignant keratinocytes and to analyze the expression patterns of p120ctn in epidermal tumor specimens. Methods: HaCaT, DJM-1, BSCC-93, HSC-1, HSC-5 and A431 cells along with normal skin tissue were subjected to RT-PCR to identify the expressed isoforms. For immunofluorescence study, surgical specimens including 29 squamous cell carcinomas (SSCs), 4 basal cell carcinomas (BCCs) and 4 seborrheic keratoses as well as 3 normal skin samples were stained with specific antibodies to detect p120ctn and E-cadherin. Results: RT-PCR revealed that the isoform 3A was predominantly expressed with faint expression of the isoform 4 and that there was no difference in expressed isoforms between the examined cell lines. Immunofluorescent staining indicated that the expression of p120ctn was significantly reduced in all of the examined squamous cell carcinomas and that p120ctn was frequently localized in cytoplasm. In benign tumors and normal samples, p120ctn was properly expressed in cell–cell boundaries. Furthermore, there were several SCCs where E-cadherin continued to be expressed with no expression of p120ctn. Conclusion: Reduced expression and aberrant localization of p120ctn are among the most common events during the development and/or progression of SCCs.