Expression of a retinoid-inducible tumor suppressor, Tazarotene-inducible gene-3, is decreased in psoriasis and skin cancer

Tazarotene-induced gene-3 (TIG-3), isolated from human keratinocytes treate d with the retinoic acid receptor-selective retinoid Tazarotene, is homolog ous to II-rev, a class II tumor suppressor. TIG-3 gene localized to chromos ome 11q23, a site of loss of heterozygosity in several malignancies, Retino ids influence epidermal differentiation and are used to treat and prevent s kin cancer. Therefore, we studied TIG-3 mRNA expression in psoriasis and in basal and SCCs by in situ hybridization and a quantitative QT-RT-PCR assay . Psoriasis lesions had significantly lower staining (median, 3) than paire d normal control skin (median, 4; P = 0.012), TIG-3 mRNA was significantly higher in normal control skin (P = 0.001), in paired adjacent skin (median, 3; P = 0.007), and in overlying epidermis (median, 3.0; P = 0.0001) than i n 21 SCC specimens as a group (median, 1.5). Aggressive SCCs (median, 1.0) were lower in TIG-3 mRNA staining than nonaggressive SCCs (median, 1.5; P = 0.07), Three aggressive tumors had no TIG-3 mRNA staining. TIG-3 protein a s shown by immunohistochemistry was highest in the suprabasal epidermis of normal skin, just under the stratum corneum, and was decreased in basal and squamous cell carcinomas, similar to the mRNA staining. Reduction in TIG-3 mRNA expression in psoriasis and basal carcinomas and loss in some aggress ive SCCs support the hypothesis that TIG-3 may function as a tumor suppress or in both normal and malignant epidermal differentiation.