Retinoids differentially regulate the proliferation of colon cancer cell lines.
In this study, the proliferative effects of retinoids were examined in the MC-26 and LoVo colon adenocarcinoma cell lines. The proliferation of the LoVo cell line was not altered in the presence of the retinoids all trans-retinoic acid (atRA) and 9-cis-retinoic acid (9-cis-RA). Both retinoids, however, stimulated the growth, as measured by cell proliferation, of MC-26 cells. atRA and 9-cis-RA were equipotent in increasing MC-26 cell proliferation, suggesting that the growth stimulation is mediated by one or more retinoic acid receptors (RARs). To determine the RAR which might be responsible for this growth stimulatory effect, we characterized the RAR subtypes which were present in both cell lines. mRNA for the RAR alpha, RAR beta, and RAR gamma were detected in the MC-26 cell. Of the RARs present in MC-26 cells, the RAR alpha does not mediate the growth stimulatory effects of retinoids, for a selective RAR alpha antagonist was unable to prevent the retinoid-induced increase in MC-26 cell growth. RAR alpha, RAR beta, and RAR gamma mRNA are also expressed in the LoVo cell line; the lack of growth-stimulation by retinoids in LoVo cells, therefore, does not seem to be due to the absence of RARs. The results obtained in these experiments demonstrate that the growth response elicited by retinoids can vary between colon cancer cells and that the differences in response may not be solely determined by the RAR subtypes which are expressed in a colon cancer cell line.
Stewart
L V
LV
Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston 77555-1031, USA.
Thomas
M L
ML
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology*; D000818:Animals; D001565:Benzoates / Q000494:pharmacology; D002117:Calcitriol / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects*; D002839:Chromans / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology*; D015870:Gene Expression / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D008297:Male; D051379:Mice; D011374:Progesterone / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D018168:Receptors, Retinoic Acid / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000072482:Retinoic Acid Receptor alpha; D012176:Retinoids / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D000097768:Retinoic Acid Receptor gamma
D001565:Benzoates; D002117:Calcitriol; D002839:Chromans; D006854:Hydrocortisone; D011374:Progesterone; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D012176:Retinoids; D000097768:Retinoic Acid Receptor gamma; C000607071:RARA protein, human; C000607072:Rara protein, mouse; C082925:retinoic acid receptor beta; C084904:Ro 41-5253