The candidate oncogene CYP24A1: A potential biomarker for colorectal tumorigenesis.

Department of Medicine, Semmelweis University, Budapest, Hungary.
Journal of Histochemistry and Cytochemistry (Impact Factor: 2.4). 11/2009; 58(3):277-85. DOI: 10.1369/jhc.2009.954339
Source: PubMed

ABSTRACT The main autocrine/paracrine role of the active metabolite of vitamin D(3), 1alpha,25-dihydroxyvitamin D(3) (1,25-D(3)), is inhibition of cell growth and induction of cell differentiation and/or apoptosis. Synthesis and degradation of the secosteroid occurs not only in the kidney but also in normal tissue or malignant extrarenal tissues such as the colon. Because 25-hydroxyvitamin D(3) 24-hydroxylase (CYP24A1) is considered to be the main enzyme determining the biological half-life of 1,25-D(3), we have examined expression of the CYP24A1 mRNA (by real-time RT-PCR) and protein (by immunohistochemistry) in normal human colon mucosa, colorectal adenomas, and adenocarcinomas in 111 patients. Although 76% of the normal and benign colonic tissue was either completely devoid of or expressed very low levels of CYP24A1, in the majority of the adenocarcinomas (69%), the enzyme was present at high concentrations. A parallel increased expression of the proliferation marker Ki-67 in the same samples suggests that overexpression of CYP24A1 reduced local 1,25-D(3) availability, decreasing its antiproliferative effect.

1 Follower
  • [Show abstract] [Hide abstract]
    ABSTRACT: VITAMIN D SYNTHESIS AND SIGNALING AFFECTS NUMEROUS CELLULAR PROCESSES INCLUDING: proliferation, differentiation and apoptosis. It is now commonly recognized that low levels of vitamin D are associated with a greater risk of tumorigenesis. Cancers of the gastrointestinal tract are most often difficult to diagnose and treat as patients typically present with progressed disease. Basic research, clinical trials and population studies have supported the concept that treatment with Vitamin D may be a therapeutic option when treating GI cancers, however treatments must be individualized and monitored closely as the side effects from Vitamin D treatment can be increasingly harmful. This review will highlight the most recent findings regarding Vitamin D signaling and GI cancers.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The major role of 24-hydroxylase (CYP24A1) is to maintain 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) homeostasis. Recently, it has been discovered that CYP24A1 also catalyses the hydroxylation of 20(OH)D3, producing dihydroxy-derivatives that show very effective antitumorigenic activities. Previously we showed a negative correlation of vitamin D receptor (VDR) and CYP27B1 expression with progression, aggressiveness and overall or disease-free survivals of skin melanomas. Therefore, we analyzed CYP24A1 expression in relation to clinicopathomorphological features of nevi, skin melanomas and metastases. In melanocytic tumors, the level of CYP24A1 was higher than in the normal epidermis. The statistically OPEN ACCESS Int. J. Mol. Sci. 2014, 15 19001 highest mean CYP24A1 level was found in nevi and early stage melanomas. With melanoma progression, CYP24A1 levels decreased and in advanced stages were comparable to the normal epidermis and metastases. Furthermore, the CYP24A1 expression positively correlated with VDR and CYP27B1, and negatively correlated with mitotic activity. Lower CYP24A1 levels correlated with the presence of ulceration, necrosis, nodular type and amelanotic phenotypes. Moreover, a lack of detectable CYP24A1 expression was related to shorter overall and disease-free survival. In conclusion, the local vitamin D endocrine system affects melanoma behavior and an elevated level of CYP24A1 appears to have an important impact on the formation of melanocytic nevi and melanomagenesis, or progression, at early stages of tumor development.
    International Journal of Molecular Sciences 10/2014; Int. J. Mol. Sci.(15):19000-19017. DOI:10.3390/ijms151019000 · 2.34 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The aims of the present study were to examine gene and protein expression of the vitamin D-inactivating 24-hyroxylase (CYP24A1) and the activating 1-alpha-hydroxylase (CYP27B1) enzyme in human papillary thyroid cancer (PTC), furthermore, to investigate the association between CYP24A1 expression and numerous clinical, histological parameters and somatic oncogene mutation status of thyroid tumor tissues.
    Journal of endocrinological investigation 09/2014; DOI:10.1007/s40618-014-0165-7 · 1.55 Impact Factor

Full-text (2 Sources)

Available from
May 16, 2014