Decreased p21 levels in anti-sense ras transfectants augments NK sensitivity.

Molecular Immunology
S K AndersonJ C Roder

Abstract

We have shown that the oncogenic EJ-ras gene, under the control of a metallothionein-I (Mt) promoter, can be induced to cause an increased susceptibility of transfected 10T1/2 fibroblasts to cytolysis mediated by natural killer (NK) cells. This effect may be specific to the ras gene family, since other oncogenes that we have tested here (src) and elsewhere (myc) do not show this effect. We have now examined the effect of modulating the level of p21 in both a positive or negative manner. The level of p21 ras was decreased by two independent mechanisms. First Zn2+ was removed from Mt-EJ-ras transformed cells. In the second approach we transfected 10T1/2 cells with a Mt-anti-sense c-H-ras construct which reduced p21 expression, slowed the growth rate and altered the morphology of 10T1/2 cells when induced with Zn. Surprisingly, the decrease in p21 ras levels by both approaches caused a marked increase in NK susceptibility (NKS) which was equivalent to that observed when the p21 ras levels were increased either by inducing EJ-ras or removing Zn2+ from Mt-anti-sense c-H-ras containing cells. The kinetics of induction of NK sensitivity due to decreasing normal p21 ras levels was identical to that observed for increasing mutated p21 r...Continue Reading

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Citations

Aug 11, 1991·Proceedings of the National Academy of Sciences of the United States of America·T A WalkerJ L Cook
Feb 5, 2008·Nature Medicine·Marco VignuzziRaul Andino
Oct 6, 1995·The Journal of Biological Chemistry·C AlbaneseR G Pestell
Feb 1, 1992·International Journal of Cancer. Journal International Du Cancer·D F ToughD A Chow

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