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

Oncogene volume 29, pages 1135–1144 (2010)Cite this article

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.

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Acknowledgements

This study was supported by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science. We thank doctors at the Department of Surgical Pathology for providing archival formalin-fixed, paraffin-embedded tissue specimens and for their pathological diagnoses, and doctors at the Department of Surgical Oncology and Gastroenterological Surgery for scientific cooperation by providing surgically resected materials in patients with breast cancer, as well as the Animal Care Facility (Sapporo Medical University School of Medicine, Sapporo, Japan).

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Authors and Affiliations

  1. Department of Pathology, Kochi University School of Medicine, Kochi, Japan

    M Osanai & G -H Lee

  2. Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan

    N Sawada

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  1. M Osanai
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  2. N Sawada
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  3. G -H Lee
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Correspondence to M Osanai.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

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Osanai, M., Sawada, N. & Lee, GH. Oncogenic and cell survival properties of the retinoic acid metabolizing enzyme, CYP26A1. Oncogene 29, 1135–1144 (2010). https://doi.org/10.1038/onc.2009.414

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