ZAC is a zinc finger transcription factor that induces apoptosis and cell cycle arrest in various cell lines. The corresponding gene is maternally imprinted and localized on chromosome 6q24-q25, a region harboring an unidentified tumor suppressor gene for a variety of solid neoplasms. ZAC expression is lost or down-regulated in some breast, ovary, and pituitary tumors and in an in vitro model of ovary epithelial cell transformation. In the present study, we examined ZAC expression in normal

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... and found a high expression level in basal keratinocytes and a lower, more heterogeneous, expression in the first suprabasal differentiating layers of epidermis. In vitro, ZAC was up-regulated following induction of keratinocyte differentiation. Conversely, ZAC expression triggered keratinocyte differentiation as indicated by induction of involucrin expression. Interestingly, we found a dramatic loss of ZAC expression in basal cell carcinoma, a neoplasm characterized by a relatively undifferentiated morphology. In contrast, ZAC expression was maintained in squamous cell carcinomas that retain the squamous differentiated phenotype. Altogether, these data suggest a role for ZAC at an early stage of keratinocyte differentiation and further support its role in carcinogenesis. (Mol Cancer Res 2005;3(9):483 -92) Received