Expression of retinoic acid receptor β in human renal cell carcinomas correlates with sensitivity to the antiproliferative effects of 13-cis-retinoic acid Journal Article

  

Authors:	Hoffman, A. D.; Engelstein, D.; Bogenrieder, T.; Papandreou, C. N.; Steckelman, E.; Dave, A.; Motzer, R. J.; Dmitrovsky, E.; Albino, A. P.; Nanus, D. M.
Article Title:	Expression of retinoic acid receptor β in human renal cell carcinomas correlates with sensitivity to the antiproliferative effects of 13-cis-retinoic acid
Abstract:	The differentiation and growth suppressive effects of retinoic acid are mediated through retinoic acid nuclear receptors (RARs and RXRs), which are ligand-activated transcription factors. Recent data suggest that both altered and regulated expression of RARs are linked to retinoic acid response in a cell context-dependent manner. This study examined the antiproliferative effects of 13-cis-retinoic acid (cRA) on 12 renal cancer cell lines and correlated these findings with the basal and induced expression of RAR-α, -β and -γ. Eleven of 12 renal cancers that were either resistant to or only minimally inhibited by cRA did not basally express RAR-β as determined by Northern blot analysis. In these cells, cRA treatment did not induce RAR-β expression. In contrast, 1 of 12 cell lines (SK-RC-06) was >90% inhibited by cRA and basally expressed RAR-β. Furthermore, RAR-β mRNA in SK-RC-06 cells was up-regulated by cRA treatment Amplification of cDNA using PCR and RAR-β isoform-specific primer pairs revealed that only SK-RC-06 cells expressed the RAR-β1 isoform. Expression of RAR-α transcripts was abundant in all 12 cell lines examined, whereas low levels of RAR-γ transcripts were detectable in 6 of 10 renal cancers. Expression of RAR-α and RAR-γ was not affected by cRA. These data showing that the majority of renal cancer cell lines are resistant to cRA suggest that: (a) resistance to the antiproliferative action of cRA correlates with repressed RAR-β mRNA expression; and (b) the anti-proliferative effects of cRA in renal cancer cells are mediated through RAR-β1.
Keywords:	controlled study; human cell; antineoplastic agents; cell division; cell differentiation; tumor cells, cultured; kidney carcinoma; kidney neoplasms; cancer resistance; gene expression regulation; cancer inhibition; carcinoma, renal cell; messenger rna; rna, messenger; isotretinoin; retinoic acid receptor; receptors, retinoic acid; blotting, southern; humans; human; priority journal; article
Journal Title:	Clinical Cancer Research
Volume:	2
Issue:	6
ISSN:	1078-0432
Publisher:	American Association for Cancer Research
Date Published:	1996-06-01
Start Page:	1077
End Page:	1082
Language:	English
PUBMED:	9816270
PROVIDER:	scopus
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-0030007752&partnerID=40&md5=bc02741187ee4b78042ff1ea99b8bc86
Notes:	Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/118834