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Expression of a Retinoid-inducible Tumor Suppressor, Tazarotene-inducible Gene-3, Is Decreased in Psoriasis and Skin Cancer¹

Section of Dermatology, Department of Internal Medical Specialties [M. D., B. H., C. S., M. C., C. H., D. DiM., P. H., B. J., J. B-M., J. Y.], Department of Head and Neck Surgery [G. C.], Division of Cancer Prevention [S. M. L.], M. D. Anderson Cancer Center, Houston, Texas 77030; Allergan Research, Irvine, California 92612 [D. DiS., R. A. S. C., S. N.]; and Department of Physiology/Biophysics, Case Western Reserve, Cleveland, Ohio 44106 [N. A. R., A. D., R. L. E.]

Tazarotene-induced gene-3 (TIG-3), isolated from human keratinocytes treated with the retinoic acid receptor-selective retinoid Tazarotene, is homologous to H-rev, a class II tumor suppressor. TIG-3 gene localized to chromosome 11q23, a site of loss of heterozygosity in several malignancies. Retinoids influence epidermal differentiation and are used to treat and prevent skin 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 paired 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 in 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 as 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 aggressive SCCs support the hypothesis that TIG-3 may function as a tumor suppressor in both normal and malignant epidermal differentiation.

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