Retinoic Acid-induced Expression of Apolipoprotein D and Concomitant Growth Arrest in Human Breast Cancer Cells Are Mediated through a Retinoic Acid Receptor RARα-dependent Signaling Pathway

López-Boado, Yolanda S.; Klaus, Michael; Dawson, Marcia I.; López-Otı́n, Carlos

doi:10.1074/jbc.271.50.32105

Cited by 33 publications

(17 citation statements)

References 48 publications

(30 reference statements)

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“…First, apc mcr mutant zebrafish lack RDHs and show profound retinoic acid deficiency phenotypes such as lack of pectoral fins and lack of jaw development (20,23). In agreement with this finding, we found that a number of retinoic acid target genes, including crbpI, crbpII, hnf4a, rarc, apoD, and meis1 were down-regulated in apc mcr mutants, whereas cyp26a1 was up-regulated (40)(41)(42)(43)(44). In addition, treatment of apc mcr mutant embryos with DEAB, a raldh2 inhibitor failed to suppress cyp26a1 levels.…”

Section: Discussionsupporting

confidence: 86%

Up-regulation of CYP26A1 in Adenomatous Polyposis Coli–Deficient Vertebrates via a WNT-Dependent Mechanism: Implications for Intestinal Cell Differentiation and Colon Tumor Development

et al. 2006

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Mutations in the adenomatous polyposis coli (APC) tumor suppressor gene seem to underlie the initiation of many colorectal carcinomas. Loss of APC function results in accumulation of B-catenin and activation of B-catenin/TCFdependent transcription. Recent studies have implicated APC in controlling retinoic acid biosynthesis during normal intestinal development through a WNT-independent mechanism. Paradoxically, however, previous studies found that dietary supplementation of Apc MIN mice with retinoic acid failed to abrogate adenoma formation. While investigating the above finding, we found that expression of CYP26A1, a major retinoic acid catabolic enzyme, was up-regulated in Apc MIN mouse adenomas, human FAP adenomas, human sporadic colon carcinomas, and in the intestine of apc mcr mutant zebrafish embryos. Mechanistically, cyp26a1 induction following apc mutation is dependent on WNT signaling as antisense morpholino knockdown of tcf4 or injection of a dnLEF construct into apc mcr mutant zebrafish suppressed expression of cyp26a1 along with known WNT target genes. In addition, injection of stabilized b-catenin or dnGSK3b into wild-type embryos induced cyp26a1 expression. Genetic knockdown or pharmacologic inhibition of cyp26a1 in apc mcr mutant zebrafish embryos rescued gut differentiation defects such as expression of intestinal fatty acid-binding protein and pancreatic trypsin. These findings support a novel role for APC in balancing retinoic acid biosynthesis and catabolism through WNT-independent and WNT-dependent mechanisms. (Cancer Res 2006; 66(15): 7571-7)

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Section: Discussionsupporting

confidence: 86%

Up-regulation of CYP26A1 in Adenomatous Polyposis Coli–Deficient Vertebrates via a WNT-Dependent Mechanism: Implications for Intestinal Cell Differentiation and Colon Tumor Development

et al. 2006

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“…Retinoic acids have antiproliferative effects in a variety of malignant cells (18,19). Similarly, we observed that the three NBL cell lines treated with ATRA show reduced cellular proliferation compared with untreated cells.…”

Section: Discussionsupporting

confidence: 54%

Retinoic Acid Induces Neuroblastoma Cell Death by Inhibiting Proteasomal Degradation of Retinoic Acid Receptor α

et al. 2004

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To seek a novel therapeutic approach to neuroblastoma (NBL), we used three NBL cell lines (SK-N-DZ, NH12, and SK-N-SH) to examine the underlining molecular mechanisms of cellular reactions and sensitivity to all-trans-retinoic acid (ATRA). SK-N-DZ cells expressed relatively high levels of retinoic acid receptor ␣ (RAR-␣) and underwent ATRA-induced cell death that was blocked by an RAR-␣ antagonist. By contrast, RAR-␣ expression gradually decreased in NH12 and SK-N-SH cells, which did not experience increased cell death in response to ATRA. We report here the ubiquitin-dependent down-regulation of RAR-␣ expression during ATRA treatment. Our data suggest that SK-N-DZ cells have a defect in RAR-␣ down-regulation, resulting in sustained high expression of RAR-␣ that confers high sensitivity to ATRA. Accordingly, treatment with a proteasome inhibitor dramatically increased ATRA-induced cell death in NH12 and SK-N-SH cell lines. Our results reveal the crucial involvement of the RAR-␣ signaling pathway in NBL cell death and show that three NBL cell lines are differentially sensitive to ATRA. These data suggest a potential novel therapy for NBL involving retinoic acid treatment combined with the inhibition of RAR-␣ degradation.

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“…Apolipoprotein D expression is regulated by RARA (55), and increased in stressed neurons of AD patients (56), as well as in normal aging, before the accumulation of neurofibrillary tangles (57). We suggest that the increased expression may be the result of feedback mechanisms dependent on the reduced amounts of retinol in aging individuals (58).…”

Section: Functions Of Retinoid-related Genesmentioning

confidence: 84%

Evidence for defective retinoid transport and function in late onset Alzheimer's disease

Goodman¹,

Pardee²

2003

Proc. Natl. Acad. Sci. U.S.A.

163

124

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The hypothesis of this article is that late onset Alzheimer's disease (AD) is influenced by the availability in brain of retinoic acid (RA), the final product of the vitamin A (retinoid) metabolic cascade. Genetic, metabolic, and environmental͞dietary evidence is cited supporting this hypothesis. Significant genetic linkages to AD are demonstrated for markers close to four of the six RA receptors, RA receptor G at 12q13, retinoid X receptor B at 6p21.3, retinoid X receptor G at 1q21, and RA receptor A at 17q21. Three of the four retinol-binding proteins at 3q23 and 10q23 and the RA-degrading cytochrome P450 enzymes at 10q23 and 2p13 map to AD linkages. Synthesis of the evidence supports retinoid hypofunction and impaired transport as contributing factors. These findings suggest testable experiments to determine whether increasing the availability of retinoid in brain, possibly through pharmacologic targeting of the RA receptors and the cytochrome P450 RAinactivating enzymes, can prevent or decrease amyloid plaque formation.

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Retinoic Acid-induced Expression of Apolipoprotein D and Concomitant Growth Arrest in Human Breast Cancer Cells Are Mediated through a Retinoic Acid Receptor RARα-dependent Signaling Pathway

Cited by 33 publications

References 48 publications

Up-regulation of CYP26A1 in Adenomatous Polyposis Coli–Deficient Vertebrates via a WNT-Dependent Mechanism: Implications for Intestinal Cell Differentiation and Colon Tumor Development

Up-regulation of CYP26A1 in Adenomatous Polyposis Coli–Deficient Vertebrates via a WNT-Dependent Mechanism: Implications for Intestinal Cell Differentiation and Colon Tumor Development

Retinoic Acid Induces Neuroblastoma Cell Death by Inhibiting Proteasomal Degradation of Retinoic Acid Receptor α

Evidence for defective retinoid transport and function in late onset Alzheimer's disease

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