Document Detail


Downregulation of Fzd6 and Cthrc1 and upregulation of olfactory receptors and protocadherins by dietary beta-carotene in lungs of Bcmo1-/- mice.
MedLine Citation:
PMID:  20472610     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
An ongoing controversy exists on beneficial versus harmful effects of high beta-carotene (BC) intake, especially for the lung. To elucidate potential mechanisms, we studied effects of BC on lung gene expression. We used a beta-carotene 15,15'-monooxygenase 1 (Bcmo1) knockout mouse (Bcmo1(-/-)) model, unable to convert BC to retinoids, and wild-type mice (Bcmo1(+/+)) mice to dissect the effects of intact BC from effects of BC metabolites. As expected, BC supplementation resulted in a higher BC accumulation in lungs of Bcmo1(-/-) mice than in lungs of Bcmo1(+/+) mice. Whole mouse genome transcriptome analysis on lung tissue revealed that more genes were regulated in Bcmo1(-/-) mice than Bcmo1(+/+) mice upon BC supplementation. Frizzled homolog 6 (Fzd6) and collagen triple helix repeat containing 1 (Cthrc1) were significantly downregulated (fold changes -2.99 and -2.60, respectively, false discovery rate < 0.05) by BC in Bcmo1(-/-). Moreover, many olfactory receptors and many members of the protocadherin family were upregulated. Since both olfactory receptors and protocadherins have an important function in sensory nerves and Fzd6 and Cthrc1 are important in stem cell development, we hypothesize that BC might have an effect on the highly innervated pulmonary neuroendocrine cell (PNEC) cluster. PNECs are highly associated with sensory nerves and are important cells in the control of stem cells. A role for BC in the innervated PNEC cluster might be of particular importance in smoke-induced carcinogenesis since PNEC-derived lung cancer is highly associated with tobacco smoke.
Authors:
Yvonne G J van Helden; Roger W Godschalk; Sandra G Heil; Annelies Bunschoten; Susanne Hessel; Jaume Amengual; M Luisa Bonet; Johannes von Lintig; Frederik J van Schooten; Jaap Keijer
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-05-14
Journal Detail:
Title:  Carcinogenesis     Volume:  31     ISSN:  1460-2180     ISO Abbreviation:  Carcinogenesis     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-08-05     Completed Date:  2010-09-13     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8008055     Medline TA:  Carcinogenesis     Country:  England    
Other Details:
Languages:  eng     Pagination:  1329-37     Citation Subset:  IM    
Affiliation:
Wageningen University, The Netherlands.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cadherins / genetics*
Carotenoids / isolation & purification
DNA Primers
Diet
Extracellular Matrix Proteins / genetics*
Frizzled Receptors / genetics*
Gene Amplification
Genome
Lung / cytology,  drug effects,  pathology,  physiology*
Male
Mice
Mice, Knockout
Oligonucleotide Array Sequence Analysis
RNA / genetics,  isolation & purification
Receptors, G-Protein-Coupled / genetics*
Receptors, Odorant / genetics*
Retinoids / isolation & purification
Up-Regulation
beta Carotene / administration & dosage,  pharmacology,  physiology*
beta-Carotene 15,15'-Monooxygenase / deficiency*
Chemical
Reg. No./Substance:
0/Cadherins; 0/Cthrc1 protein, mouse; 0/DNA Primers; 0/Extracellular Matrix Proteins; 0/Frizzled Receptors; 0/Fzd6 protein, mouse; 0/Receptors, G-Protein-Coupled; 0/Receptors, Odorant; 0/Retinoids; 36-88-4/Carotenoids; 63231-63-0/RNA; 7235-40-7/beta Carotene; EC 1.14.99.36/Bcmo1 protein, mouse; EC 1.14.99.36/beta-Carotene 15,15'-Monooxygenase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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