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Liver Cancer in Transgenic Mice Carrying the Human Immunodeficiency Virus tat Gene¹

Laboratory of Virology, Jerome H. Holland Laboratory, American Red Cross, Rockville, Maryland 20855 [J. V., L. A. N., L. N., G. J.], and Department of Medical Pathology, University of California, School of Medicine, Davis, California 95616 [S. H. H.]

Patients with the acquired immunodeficiency syndrome are at risk to develop a variety of different cancers. Based on epidemiological data, Kaposi's sarcoma and non-Hodgkin's lymphoma have been clearly associated with infection by the human immunodeficiency virus (HIV). Additional cancers such as basal cell and squamous cell carcinomas, melanoma, and hepatocellular carcinoma have also been reported to be associated with a diagnosis of acquired immunodeficiency syndrome. A direct causal role of HIV has yet to be established for any of these cancers. We now report that transgenic mice carrying the HIV tat gene develop a high incidence of hepatocellular carcinoma after a long latency and that these changes in the liver are likely to be initiated by extrahepatic growth signals from the tat expressing cells in these mice. We predict that as acquired immunodeficiency syndrome patients begin to respond to therapy and show prolonged survival, such "secondary" malignancies induced by HIV will become increasingly prevalent.

¹ This work was supported by NIH Grants CA53633 and CA52408.

² To whom requests for reprints should be addressed.

Received 8/ 5/91. Accepted 10/ 7/91.

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