Human Kaposi's sarcoma cell-mediated tumorigenesis in human immunodeficiency type 1 Tat-expressing transgenic mice

Abstract

Background: The human immunodeficiency virus type 1 (HIV-1) transactivator (Tat) protein has been linked to the development and course of Kaposi's sarcoma (KS) associated with acquired immunodeficiency disease syndrome (AIDS-KS). Tat is an 86-101 amino-acid protein encoded by two exons. To evaluate the growth-promoting effects of Tat in AIDS-KS in vivo, we developed transgenic mice expressing the one-exon-encoded 72 amino-acid protein (Tat72) and the two-exon-encoded 86 amino-acid protein (Tat86). Methods: Human KS SLK cells were injected subcutaneously into CD4+ T-cell- depleted male mice, and the tumors that formed after 3-4 weeks were recovered and analyzed for the expression of Tat protein(s), different cytokine messenger RNAs (mRNAs), and matrix metalloproteinases (MMPs). All statistical tests were two-sided. Results: The average tumor weight was maximum in Tat86 mice (~600 mg) compared with Tat72 (~200 mg) and nontransgenic (~100 mg) mice (P