Oncogenic Properties of HIV-Tat in Colorectal Cancer Cells

Abstract

With the advent of Highly-Active-Anti-Retroviral-Therapy (HAART), HIV patients can expect to live beyond 10-15 years following diagnosis. An unexpected result of increased survival is the emergence of opportunistic, oncogenic virus-associated cancers such as Burkitt's lymphoma (Epstein-Barr Virus), cervical cancer (Human Papilloma Virus) and Kaposi's sarcoma (Kaposi's sarcoma-associated herpesvirus) in this immuno-compromised population. Furthermore, there are reports of colorectal cancers (CRC) in long-term HIV-AIDS survivors. Compared to the general, non-immuno-compromised population, long-term AIDS patients have 4 and 3.3-fold increased risk of developing colorectal and anorectal cancer respectively. Unlike oncogenic virus-associated cancers, CRC is not known to have a viral etiology. Our study aimed to investigate one aspect of HIV infection and colorectal carcinogenesis. We proposed that the HIV transactivator protein Tat; a protein with known oncogenic properties that is secreted and can re-enter non-infected cells may have a role in CRC. Using two CRC cell lines, LIM1215 and LIM2537 we found that Tat inhibits epithelial cyto-differentiation, blocks apoptosis in vitro and accelerates tumour formation in vivo. In addition, Tat significantly increases in vitro migration in the absence of foetal calf serum. These properties underpin CRC, and as HIV infection is initiated in the gut lymphoid system, these data provide a basis for the increased incidence of CRC in long term AIDS patients.

Characteristics of non‐AIDS‐defining malignancies in the HAART era: a clinico‐epidemiological study

“…Direct oncogenic effects of the virus itself could also be implied. Indeed, in vitro experiments suggest that the tat HIV protein could interfere with DNA repair mechanisms and apoptosis increasing the risk of malignant transformation in the host cells [33,34]. However, clinical studies are discordant about the risk of NADM and their relation to HIV viral load.…”

Roles and functions of HIV-1 Tat protein in the CNS: an overview

“…In the context of HIV-Associated Nephropathy, Tat protein increased albumin permeability and rapidly induced the redistribution and loss of nephrin in isolated glomeruli [107]. Furthermore, studies investigating other HIV-Associated conditions such as HIV-Associated Thrombocytopenia, Pulmonary vesicular remodeling as well as Cancer development suggest that HIV-1Tat protein plays significant role in the pathological progression of those diseases [108-111]. …”

HIV-1 Tat and AIDS-associated cancer: targeting the cellular anti-cancer barrier?

“…Colorectal cancer does not have a known viral etiology. Interestingly, Tat may play a role in development of this type of cancer in HIV-1-infected patients [ 23 ]. The mechanism underlying this effect of Tat has to be yet fully elucidated and we present below one possible mechanism how Tat may affect cellular processes, which are closely related to cancer development.…”