THE HIV TAT GENE IS A PROMOTER OF EPIDERMAL SKIN TUMORS

Human immunodeficiency virus (HIV) infected patients have a very high incidence (>90%) of neoplastic and non-neoplastic skin disorders. The proliferative lesions frequently involve the epidermis and include squ amous and basal cell carcinomas, and the papulosquamous diseases of se borrheic dermatitis and psoriasis. Although the role played by HIV in the development of these proliferative skin lesions is not clear, ther e are several lines of evidence suggesting that HIV may play a causati ve role. We show that transgenic mice carrying the HIV tat gene under the control of the viral LTR constitutively express the tnt gene in ke ratinocytes. When a single subthreshold dose of a carcinogen initiator is topically applied to these mice, tumor promoters are no longer req uired to induce the development of epidermal skin tumors, suggesting t hat Tat expression in keratinocytes is capable of substituting for pho rbol ester tumor promoters in the two-step carcinogenesis skin cancer model. Together, Tat and phorbol ester have additive effects in promot ing tumors in transgenic mice first initiated with carcinogens. We con clude that although Tat alone is insufficient to cause epidermal tumor s, it functions as a tumor promoter and predisposes these mice to deve lop tumors following an initiating event.