- Email: [email protected]
Aspirin induces apoptosis in colorectal cancer cells
NEWS A cofactor for HIV-1 by Edward A Berger Bethesda, USA) has protein, fusin, that works
team led
rY(NIH, identified
a
in combination with cell-surface CD4 HIV-11 to infect cells to enable 272: 872-77). It has 1996; (Science been known for a decade that nonhuman cells expressing human CD4 require an additional cofactor to induce fusion of cell and viral membranes and so permit HIV-11 entry (figure), and there has been strong competition between researchers to identify this cofactor. To find the gene for fusin, Berger et al designed a novel assay that measures the ability of cells expressing HIV-1envelope (env) protein on their surface (playing the role of HIV virions) to fuse with non-human cells expressing human CD4. The envexpressing cells contain a bacterial reporter gene LacZ (coding for betagalactosidase), linked to the T7 promoter, while the T7 RNA polymerase gene, which is necessary for the expression of the reporter gene, is contained in the CD4-expressing cells. Because the reporter and the polymerase are initially in separate cells, the beta-galactosidase gene is expressed only if the two cells fuse. cDNA obtained from human cells permissive for HIV-1 infection is introduced into the CD4-expressing cell line, and when the cDNA coding for the missing cofactor is among the sequences introduced, cell fusion occurs, the T7 polymerase activates the LacZ gene, which is detected by a colour reaction. The gene responsible for fusion can then be isolated. It turns out that fusin has already been cloned by several laboratories
entry into cells is identified
seeking new members of the superfamily of 7-transmembrane-segment, G-protein-linked receptors, but no role
in
HIV-11
Results help
to
explain why regular aspirin
intake seems to reduce the risk of colorectal cancer by 50%. Christos
Paraskeva
et al (Bristol, UK) treated human colorectal cell lines
was
fied but the closest known homologues of fusin are the IL-8 receptor and the angiotensin II receptor. The possible connection with IL-8, a chemokine (chemoattractant cytokine), is intriguing because
Robert C Gallo (Baltimore, USA) and Paolo Lusso (Milan, Italy) have reported that three chemokines produced by CD8-positive cells suppress HIV infection in cultured cells (Science 1995; 270: 1811-15). In the light of the present results, the chemokines may do this by binding to fusin or otherwise interfering with its function in HIV-1entry into cells Fusin facilitates infection of blood with monocytes peripheral T-cell-line tropic strains of HIV-11 (which tend to occur late in HIV-1 infection, after the onset of frank AIDS), but does not facilitate infection of monocytes with macrophage-
Aspirin induces apoptosis in colorectal published in the May issue of Cancer Research may
infection
previously suspected. The natural ligand for fusin has not been identi-
(adenoma,
cancer
strains of HIV-1, which are the strains that normally initiate human infection. Presumably, macrophagetropic strains (and perhaps also the other immunodeficiency viruses such as HIV-2 and SIV) require a distinct fusin-like cofactor for entry into cells. Whether the discovery of fusin will lead to a clinically useful strategy for blocking the interaction of fusin with HIV envelope protein is not clear. Fusin is a protein normally expressed
tropic
on cells and the effects of blocking its action are unknown as yet. By analogy, blocking CD4 has not proved generally useful in AIDS treatment because of the resultant immunosuppression. One immediate implication of the identification of fusin for AIDS research will be that researchers it at last be able to construct small-animal models of AIDS. For example, rabbit cells support all post-entry steps in the HIV-1 replication cycle, and rabbits transgenic for both human CD4 and fusin may also now be infectable with HIV-1.
Paul M Rowe
cells
in-vitro-transformed
adenoma, and carcinoma cell lines) with sodium salicylate and found that while they all arrested in Go of the cell cycle, apoptosis increased most significantly in in-vitrotransformed adenoma cells and in
carcinoma cells. The researchers do know yet why cells at later stages of neoplastic development are induced to apoptose, but tipping the scales towards cell death may explain the effect of aspirin on colorectal cancer risks. D
not
1395
team led
rY(NIH, identified
a
in combination with cell-surface CD4 HIV-11 to infect cells to enable 272: 872-77). It has 1996; (Science been known for a decade that nonhuman cells expressing human CD4 require an additional cofactor to induce fusion of cell and viral membranes and so permit HIV-11 entry (figure), and there has been strong competition between researchers to identify this cofactor. To find the gene for fusin, Berger et al designed a novel assay that measures the ability of cells expressing HIV-1envelope (env) protein on their surface (playing the role of HIV virions) to fuse with non-human cells expressing human CD4. The envexpressing cells contain a bacterial reporter gene LacZ (coding for betagalactosidase), linked to the T7 promoter, while the T7 RNA polymerase gene, which is necessary for the expression of the reporter gene, is contained in the CD4-expressing cells. Because the reporter and the polymerase are initially in separate cells, the beta-galactosidase gene is expressed only if the two cells fuse. cDNA obtained from human cells permissive for HIV-1 infection is introduced into the CD4-expressing cell line, and when the cDNA coding for the missing cofactor is among the sequences introduced, cell fusion occurs, the T7 polymerase activates the LacZ gene, which is detected by a colour reaction. The gene responsible for fusion can then be isolated. It turns out that fusin has already been cloned by several laboratories
entry into cells is identified
seeking new members of the superfamily of 7-transmembrane-segment, G-protein-linked receptors, but no role
in
HIV-11
Results help
to
explain why regular aspirin
intake seems to reduce the risk of colorectal cancer by 50%. Christos
Paraskeva
et al (Bristol, UK) treated human colorectal cell lines
was
fied but the closest known homologues of fusin are the IL-8 receptor and the angiotensin II receptor. The possible connection with IL-8, a chemokine (chemoattractant cytokine), is intriguing because
Robert C Gallo (Baltimore, USA) and Paolo Lusso (Milan, Italy) have reported that three chemokines produced by CD8-positive cells suppress HIV infection in cultured cells (Science 1995; 270: 1811-15). In the light of the present results, the chemokines may do this by binding to fusin or otherwise interfering with its function in HIV-1entry into cells Fusin facilitates infection of blood with monocytes peripheral T-cell-line tropic strains of HIV-11 (which tend to occur late in HIV-1 infection, after the onset of frank AIDS), but does not facilitate infection of monocytes with macrophage-
Aspirin induces apoptosis in colorectal published in the May issue of Cancer Research may
infection
previously suspected. The natural ligand for fusin has not been identi-
(adenoma,
cancer
strains of HIV-1, which are the strains that normally initiate human infection. Presumably, macrophagetropic strains (and perhaps also the other immunodeficiency viruses such as HIV-2 and SIV) require a distinct fusin-like cofactor for entry into cells. Whether the discovery of fusin will lead to a clinically useful strategy for blocking the interaction of fusin with HIV envelope protein is not clear. Fusin is a protein normally expressed
tropic
on cells and the effects of blocking its action are unknown as yet. By analogy, blocking CD4 has not proved generally useful in AIDS treatment because of the resultant immunosuppression. One immediate implication of the identification of fusin for AIDS research will be that researchers it at last be able to construct small-animal models of AIDS. For example, rabbit cells support all post-entry steps in the HIV-1 replication cycle, and rabbits transgenic for both human CD4 and fusin may also now be infectable with HIV-1.
Paul M Rowe
cells
in-vitro-transformed
adenoma, and carcinoma cell lines) with sodium salicylate and found that while they all arrested in Go of the cell cycle, apoptosis increased most significantly in in-vitrotransformed adenoma cells and in
carcinoma cells. The researchers do know yet why cells at later stages of neoplastic development are induced to apoptose, but tipping the scales towards cell death may explain the effect of aspirin on colorectal cancer risks. D
not
1395