Adducin expression in cutaneous and oral lesions: alpha- and beta-adducin transcripts down-regulate with keratinocyte...

Adducin is a heterodimer of alpha- with beta- or gamma-subunits that regulates the assembly of the spectrin-based membrane skeleton in erythrocytes. Although adducin has been identified in various non-erythroid cells and tissues, it has been localized at intercellular junctions only in keratinocytes and epidermis. However, no data are available yet on the regulation of individual adducin genes in differentiating versus hyperproliferating keratinocytes. Due to the unavailability of mono-specific antibodies for individual adducins, this study has used RT-PCR and in situ hybridization to investigate the expression of alpha- and beta-adducins in cultured cells and in stratified epithelia including cutaneous and oral lesions. Using RT-PCR, the alpha-transcripts were consistently expressed in all cell lines tested, as well as in normal interfollicular epidermis, whereas the beta-transcripts were more variable and were strongly expressed in K562, A431, and primary keratinocytes. However, in normal skin, oral mucosa, and attached gingivae, the levels of alpha-transcripts closely paralleled those for the beta-subunit. In most normal tissues, adducin expression was observed primarily in the proliferating compartments including the basal layer and lower suprabasal layers. Expression of both genes was also up-regulated in skin diseases characterized by increased cell proliferation and keratinocyte activation, such as basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and psoriasis. It was observed that, in most cases, the expression of both alpha- and beta-adducin was accompanied by increased expression of the proliferation marker Ki-67 and keratins K6 and K16. Differentiating keratinocytes in normal epithelia as well as in tumours appear to suppress the expression of adducin transcripts. The data suggest that the expression of adducin genes may be linked to cell proliferation and starts to down-regulate at the onset of differentiation.