NEW YORK (Reuters Health) - Blocking of receptor interacting protein 140 (RIP 140) appears to boost the inhibitory action of retinoic acid (RA) on cancer cells, researchers report in the November 7th issue of the Journal of Biological Chemistry.
Dr. Michael J. Spinella of Dartmouth Medical School, Hanover, New Hampshire and colleagues, observe that in earlier work they showed that the ligand-dependent co-repressor RIP 140 is a direct transcriptional target of retinoic acid. They also note that it is “one of the most enigmatic nuclear receptor coregulators.”
In the current study, the team suggests that retinoic acid induction of RIP 140 serves as a negative feedback signal that limits retinoic acid activity at the level of nuclear receptor coregulation.
In work with human embryonal carcinoma cells, the investigators established that silencing of RIP 140 induction by retinoic acid, “dramatically enhances and accelerates retinoid receptor transactivation.” This was also seen with endogenous expression of other retinoic acid target genes and retinoic acid-induced neuronal differentiation and cell cycle arrest.
“When we knocked RP140 out of the cancer cells,” Dr. Spinella said in a statement, “they began to differentiate within 2 days; it usually takes 5 days to see any change in the cells.”
“If we can understand all the rate-limiting steps for how retinoids slow cancer growth,” he concluded, “we will be in a much better position to control the process and inhibit cancer more effectively.”
Source: J Biol Chem 2003;278:43889-43892. [ Google search on this article ]
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