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Expression and Splice Variants of Beta‐Carotene 9′, 10′‐Oxygenase: Relevance for Tissue‐Specific Metabolism of Provitamin a Carotenoids and Lycopene
Author(s) -
Gong Wen Rong,
Gong Xiao Min,
Zaripheh Susan,
Rubin Lewis P
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1060-b
Subject(s) - biology , retinoic acid , lncap , gene expression , retinoid , beta carotene , gene isoform , carotenoid , microbiology and biotechnology , biochemistry , gene , cancer cell , genetics , cancer
Retinoid acid (RA) is essential for growth, vision, reproduction, embryonic development, epithelial differentiation, and immune response. In addition, carotenoids, lycopene and/or RA and synthetic retinoids have used as agents in cancer prevention and therapy. Beta‐carotene 9′, 10′‐dioxygenase (CMO2) is an alternative enzymatic pathway for metabolizing certain provitamin A carotenoids to produce retinal and RA. Recent data from our lab and others suggests CMO2 also is a key mediator of lycopene metabolism and activity. Hence, this gene may play a role in lycopene sensitivity of tumor cells. These observations prompted us to: ( 1 ) characterize CMO2 gene expression in various human cell lines and tissues and ( 2 ) determine the expression of predicted CMO2 isoforms and splice variants. Methods Using RT‐PCR, we investigated CMO2 expression in human hepatic HepG2, pulmonary alveolar epithelial A459, macrophage‐like THP‐1 cells and several prostatic cell lines (LNcaP, C4‐2, CuR4, DU145, PC3). The expression mapped PCR amplicons were verified by DNA sequencing. Results We found CMO2 expression is detectable at different levels in all cell lines studied. We also demonstrated the existence of a cell type specific CMO2 alternatively spliced mRNA that lacks 3 exons present in the full length CMO2 message. The deduced protein structure of both isoforms has been subjected to molecular modeling. The existence of CMO2 isoforms suggests a complex role for carotenoid metabolism in normal and neoplastic cellular function. (NIH HD42174, RR18728).