Oncogenic properties of HIV-Tat in colorectal cancer cells.
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.
Huynh
Duy
D
Peter MacCallum Cancer Centre, East Melbourne Vic, Australia.
Vincan
Elizabeth
E
Mantamadiotis
Theo
T
Purcell
Damian
D
Chan
Chee-Kai
CK
Ramsay
Robert
R
D000818:Animals; D015197:Carcinogenicity Tests; D002454:Cell Differentiation / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement; D015179:Colorectal Neoplasms / Q000821:virology*; D015696:Gene Products, tat / Q000502:physiology*; D015658:HIV Infections / Q000150:complications*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D051379:Mice; D014183:Transplantation, Heterologous; D054322:tat Gene Products, Human Immunodeficiency Virus
D015696:Gene Products, tat; D054322:tat Gene Products, Human Immunodeficiency Virus