Retinoid Signaling Manipulation May Aid Cancer Therapy
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 ]
MeSH Headings: Biological Sciences : Biology : Environment and Public Health : Gene Expression Regulation : Genetics : Genetics, Biochemical : Health : Health Occupations : Health Services Administration : Medicine : Molecular Biology : Population Characteristics : Preventive Medicine : Public Health : Quality of Health Care : Specialties, Medical : Epidemiologic Factors : Causality : Health Care Quality, Access, and Evaluation : Biological Sciences : Health Care
Copyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.