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Lee MO, Han SY, Jiang S, Park JH, Kim SJDifferential effects of retinoic acid on growth and apoptosis in human colon cancer cell lines associated with the induction of retinoic acid receptor beta. Biochem Pharmacol 59: 485-496

Institute for Immunology and Immunological Diseases, Yonsei University, Sŏul, Seoul, South Korea
Biochemical Pharmacology (Impact Factor: 4.65). 04/2000; 59(5):485-96. DOI: 10.1016/S0006-2952(99)00355-X
Source: PubMed

ABSTRACT Retinoids are well known as potential chemopreventive and chemotherapeutic agents against a variety of human cancers. Here, we report that retinoic acid (RA) induced differential growth inhibition in human colon cancer cell lines: while DLD-1, HT-29, and WiDr were relatively resistant, HCT-15 and Colo201 were relatively sensitive. All-trans-retinoic acid caused morphological and biochemical changes such as membrane shrinkage, chromatin condensation, and DNA cleavage, which are typical features of cells undergoing apoptosis in sensitive cell lines. Although retinoic acid receptor (RAR)alpha, beta, gamma and retinoid X receptor alpha were expressed in all cell lines examined, a significant induction of RARbeta by all-trans-RA was observed only in sensitive cell lines, suggesting important roles of RARbeta in RA sensitivity. When a vector containing the RARbeta gene was introduced into a relatively resistant cell line, DLD-1, the cells acquired RA sensitivity. Further, we found that the RARbeta transfectants of DLD-1 expressed an enhanced level of c-Myc and Bax proteins, which may result in the increased susceptibility of the cells to all-trans-RA-induced apoptosis. In summary, our data demonstrated that RA induced growth inhibition and apoptosis in human colon cancer cells and that the induction of RAR3 may mediate the retinoid action.

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    • "This is in agreement with previous reports, which have shown that RAR-β expression is generally low or absent in pancreatic cancer cells (Kaiser et al, 1997). Although induction of RAR-β has been reported to be an indicator of retinoid response (Seewaldt et al, 1995; Lee et al, 2000; Sun et al, 2000), we could detect no induction of either RAR subtype upon retinoid treatment. This may seem surprising, but is likely to be due to methylation of the RAR-beta gene (Ueki et al, 2000). "
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