Oncogenic and cell survival properties of the retinoic acid metabolizing enzyme, CYP26A1

M Osanai; N Sawada; G-H Lee

doi:10.1038/onc.2009.414

Oncogenic and cell survival properties of the retinoic acid metabolizing enzyme, CYP26A1

Oncogene. 2010 Feb 25;29(8):1135-44. doi: 10.1038/onc.2009.414. Epub 2009 Nov 23.

Authors

M Osanai¹, N Sawada, G-H Lee

Affiliation

¹ Department of Pathology, Kochi University School of Medicine, Nankoku, Kochi, Japan. osanaim@kochi-u.ac.jp

PMID: 19935721
DOI: 10.1038/onc.2009.414

Abstract

Vitamin A deficiency (VAD) is associated with increased susceptibility to carcinogenesis in animal models and elevated risk for a number of human cancers. Here, we found that CYP26A1, the gene encoding a cytochrome P450 enzyme specifically involved in metabolic inactivation of retinoic acid (RA), the most active vitamin A derivative, is highly expressed in 42% (27/65) of primary breast cancers. We also showed that enhanced expression of CYP26A1 suppresses cellular responses to anoikis and consequently promotes anchorage-independent growth. This transformed phenotype was sufficient to markedly increase tumorigenic and metastatic potential. Suppression of CYP26A1 significantly reversed the CYP26A1-mediated oncogenic characteristics, suggesting a direct link between intracellular RA status and tumorigenicity. Our observations provide strong evidence for oncogenic and cell survival properties of CYP26A1 in carcinogenesis, and suggest mechanisms whereby VAD might promote cancer development.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Anoikis / drug effects*
Breast Neoplasms / enzymology
Breast Neoplasms / etiology*
Breast Neoplasms / metabolism
Carcinogenicity Tests
Carcinogens / metabolism
Carcinogens / pharmacology*
Cell Proliferation / drug effects
Cell Survival / drug effects
Cell Transformation, Neoplastic / drug effects*
Cell Transformation, Neoplastic / pathology
Cytochrome P-450 Enzyme System / metabolism
Cytochrome P-450 Enzyme System / pharmacokinetics
Cytochrome P-450 Enzyme System / pharmacology*
Cytochrome P-450 Enzyme System / physiology
Disease Models, Animal
Drug Interactions
Gene Expression Profiling
Humans
Mice
Mice, Knockout
Neoplasms / etiology
Retinoic Acid 4-Hydroxylase
Reverse Transcriptase Polymerase Chain Reaction
Tretinoin / metabolism
Tretinoin / pharmacology*
Tumor Cells, Cultured
Vitamin A / pharmacology*
Vitamin A Deficiency / complications*

Substances

Carcinogens
Vitamin A
Tretinoin
Cytochrome P-450 Enzyme System
Cyp26a1 protein, mouse
Retinoic Acid 4-Hydroxylase