Important note: Information in this article was accurate in 1995. The state of the art may have changed since the publication date.
HIV tat protein can regulate promoters of the insulin-like growth factor II gene in cultured leiomyosarcoma cells (Meeting abstract).
Proc Annu Meet Am Assoc Cancer Res; 14:A824 1995. Unique Identifier : AIDSLINE ICDB/95613976 Hirschfeld S; Helman LJ; Molecular Oncology Section, Pediatric Branch, National Cancer; Institute, Bethesda, MD 20892
Abstract:
Among the complications of HIV infection in children is an unusually high incidence of tumors of smooth muscle origin. Similar to other tumors of mesenchyme derived tissue, leiomyomas and leiomyosarcomas have been shown to over express cellular growth factors, in particular, insulin-like growth factor II (IGF-II). The IGF-II gene has four promoters which have been shown to be both tissue and developmentally specific. Two of these promoters, P3 and P4, regulate mRNA species that are prevalent in tumor tissue. We hypothesized that part of the etiology of the smooth muscle tumors in the context of HIV infection may be due to viral gene products. The protein tat is a regulator of transcription for viral and a number of cellular genes, including both the ligand and receptor for several cytokines. Furthermore, tat can be secreted and taken up by cells. We examined the effects of tat in transient transfection assays using a tat expression vector and the P3 and P4 IGF-II promoters linked to a luciferase reporter gene. A leiomyosarcoma cell line, HTB 88, that expresses little or no IGF-II mRNA, was transfected, and luciferase activity measured after 72 hours. When tat was added, both promoters showed up to a 12-fold increase in activity with P3 showing greater relative activation than P4. These results suggest a potential mechanism whereby an HIV gene product can increase the expression of IGF-II, which may play a critical role in the development of smooth muscle tumors.
Keywords: Child *Gene Expression Regulation, Neoplastic Gene Expression Regulation, Viral Gene Products, tat/BIOSYNTHESIS/*METABOLISM Genetic Vectors Human HIV/*METABOLISM Insulin-Like Growth Factor II/BIOSYNTHESIS/*GENETICS Leiomyosarcoma Luciferase/BIOSYNTHESIS *Promoter Regions (Genetics) Recombinant Proteins/BIOSYNTHESIS/METABOLISM Transfection Tumor Cells, Cultured ABSTRACT 951230
M95C3224
AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.