Reduction of both RAR and RXR levels is required to maximally alter sensitivity of CA-OV3 ovarian tumor cells to growth suppression by all-trans-retinoic acid

Experimental Cell Research
S WuK J Soprano

Abstract

We wished to determine the effect of altering the levels or functional activity of retinoid receptors, in particular retinoic acid receptor-alpha (RAR-alpha) and retinoid X receptor-alpha (RXR-alpha) on the growth sensitivity of ovarian tumor cells to all-trans-retinoic acid (all-trans-RA). We found that CA-OV3 cells could be made resistant to all-trans-RA growth inhibition by overexpressing RAR-beta(R269Q), an efficient dominant negative mutant which inhibits the function of all RAR subtypes. Antisense technology was then used to prepare stable transfectants of the retinoid-sensitive ovarian carcinoma cell line CA-OV3 in which expression of RAR-alpha, RXR-alpha, or both RAR-alpha and RXR-alpha was reduced. The effect of all-trans-RA on ovarian tumor cell growth was determined by MTT assay, autoradiographic analysis of DNA synthesis, and anchorage-independent colony formation in soft agar. Our results show that cell lines expressing reduced levels of either RAR-alpha alone or RXR-alpha alone exhibited a small decrease in sensitivity to growth inhibition by all-trans-RA. However, maximum RA resistance was obtained in cell lines in which the levels of both RAR-alpha and RXR-alpha were reduced. These results demonstrate the import...Continue Reading

Citations

Aug 15, 2000·Journal of Cellular Physiology·D ZhangK J Soprano
Jan 6, 2018·International Journal of Molecular Sciences·Petr ChlapekRenata Veselska
Apr 20, 2004·Journal of Cellular Physiology·William F HolmesKenneth J Soprano
Mar 30, 2006·International Journal of Cancer. Journal International Du Cancer·Molly BrewerChangping Zou
Dec 7, 2002·The Journal of Nutrition·Kenneth J Soprano, Dianne Robert Soprano

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