Suppression of mammary carcinoma growth by retinoic acid: proapoptotic genes are targets for retinoic acid receptor and cellular retinoic acid-binding protein II signaling.
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Donato LJ, Noy N
Suppression of mammary carcinoma growth by retinoic acid: proapoptotic genes are targets for retinoic acid receptor and cellular retinoic acid-binding protein II signaling.
Cancer Res. 2005 Sep 15;65(18):8193-9.
- PubMed ID
- 16166294 [ View in PubMed]
- Abstract
Retinoic acid (RA) displays pronounced anticarcinogenic activities in several types of cancer. Whereas the mechanisms that underlie this activity remain incompletely understood, tumor suppression by RA is believed to emanate primarily from its ability to regulate transcription of multiple target genes. Here, we investigated molecular events through which RA inhibits the growth of MCF-7 mammary carcinoma cells, focusing on the involvement of the two proteins that mediate transcriptional activation by RA, the nuclear hormone receptor retinoic acid receptor (RAR) and the cellular retinoic acid-binding protein (CRABP) II, in this process. RA treatment of MCF-7 cells did not affect cell cycle distribution but triggered pronounced apoptosis. Accordingly, expression array analyses revealed that RA induces the expression of several proapoptotic genes, including caspase 7 and caspase 9. Whereas caspase 7 is an indirect responder to RA signaling, caspase 9 is a novel direct target for RAR, and it harbors a functional retinoic acid response element in its second intron. In agreement with the known role of CRABP-II in enhancing the transcriptional activity of RAR, the binding protein augmented RA-induced up-regulation of caspase 9, cooperated with RA in activating both caspase 7 and 9, and amplified the ability of RA to trigger apoptosis. Surprisingly, the data indicate that CRABP-II also displays proapoptotic activities on its own. Specifically, overexpression of CRABP-II, in the absence of RA, up-regulated the expression of Apaf1 and triggered caspase 7 and caspase 9 cleavage. These observations suggest that, in addition to its known role in direct delivery of RA to RAR, CRABP-II may have an additional, RA-independent, function.
DrugBank Data that Cites this Article
- Drug Carriers
Drug Carrier Kind Organism Pharmacological Action Actions Alitretinoin Cellular retinoic acid-binding protein 2 Protein Humans UnknownAgonistDetails - Pharmaco-transcriptomics
Drug Drug Groups Gene Gene ID Change Interaction Chromosome Tretinoin Approved Investigational Nutraceutical CASP7 840 upregulated Tretinoin results in increased expression of CASP7 mRNA 10q25.3 Tretinoin Approved Investigational Nutraceutical CASP9 842 upregulated Tretinoin results in increased expression of CASP9 mRNA 1p36.21 Tretinoin Approved Investigational Nutraceutical IRF1 3659 upregulated Tretinoin results in increased expression of IRF1 mRNA 5q31.1 Tretinoin Approved Investigational Nutraceutical TIA1 7072 upregulated Tretinoin results in increased expression of TIA1 mRNA 2p13.3 Tretinoin Approved Investigational Nutraceutical TNFRSF1A 7132 upregulated Tretinoin results in increased expression of TNFRSF1A mRNA 12p13.31