THE HIV TAT GENE IS A PROMOTER OF EPIDERMAL SKIN TUMORS

Abstract

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 squamous and basal cell carcinomas, and the papulosquamous diseases of seborrheic dermatitis and psoriasis. Although the role played by HIV in the development of these proliferative skin lesions is not clear, there are several lines of evidence suggesting that HIV may play a causative role. We show that transgenic mice carrying the HIV tat gene under the control of the viral LTR constitutively express the tnt gene in keratinocytes. When a single subthreshold dose of a carcinogen initiator is topically applied to these mice, tumor promoters are no longer required to induce the development of epidermal skin tumors, suggesting that Tat expression in keratinocytes is capable of substituting for phorbol ester tumor promoters in the two-step carcinogenesis skin cancer model. Together, Tat and phorbol ester have additive effects in promoting tumors in transgenic mice first initiated with carcinogens. We conclude that although Tat alone is insufficient to cause epidermal tumors, it functions as a tumor promoter and predisposes these mice to develop tumors following an initiating event.