Retinoic acid metabolizing enzyme CYP26A1 is a candidate oncogene, and a possible therapeutic target for cancers.

在动物模型中，维生素A缺乏症（VAD）与致癌易感性增加和许多人类癌症风险增加有关。我们发现，CYP26A1基因编码的细胞色素P450酶特异性参与维甲酸（RA）的代谢失活，维甲酸是最活跃的维生素a衍生物，在多种类型的癌症中，包括原发性乳腺癌中都有高表达。我们还发现，CYP26A1表达增强导致RA生物利用度降低的状态足以显著增加致瘤性和转移潜力。我们的观察结果为CYP26A1在癌变过程中的致癌和细胞存活特性提供了强有力的证据，并提出了VAD可能促进癌症发展的机制。我们认为特异性药物介导的CYP26A1失活可能对人类肿瘤的恶性潜能有显著影响，这些结果表明其在CYP26A1抑制癌症治疗中的潜在可行性。

Vitamin A deficiency (VAD) is associated with increased susceptibility to carcinogenesis in animal models and elevated risk for a number of human cancers. We found that the 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 a number of variety types of cancer, including primary breast carcinomas. We also found that the state of reduced RA bioavailability caused by enhanced expression of CYP26A1 is sufficient to markedly increase tumorigenic and metastatic potential. Our observations provide strong evidence for oncogenic and cell survival properties of CYP26A1 in carcinogenesis, and suggest mechanisms whereby VAD might promote cancer development. We believe that specific drug-mediated inactivation of CYP26A1 may have a notable impact on malignant potential of human tumors, and these results show its potential feasibility of CYP26A1-inhibitory cancer therapies.