Clinical significance of the overexpression of the candidate oncogene CYP24 in esophageal cancer.

Abstract

BACKGROUND:

By using array comparative genomic hybridization (CGH), the increased copy number of CYP24 (which encodes vitamin D 24-hydroxylase) at 20q13.2 was previously reported, leading to the identification of CYP24 as a candidate oncogene in breast cancer. CYP24 leads to abrogate growth control mediated by vitamin D.

MATERIALS AND METHODS:

We examined CYP24 expression as well as VDR (vitamin D receptor) gene expression in 42 esophageal cancer cases using semi-quantitative RT-PCR assay. We induced CYP24 in seven esophageal cancer cell lines using 25-hydroxyvitamin D3 [25(OH)D3] and compared cell growth rate, measured using the 3-(4, 5-dimethylthiazol-2-y)-2, 5-diphenyltetrazolium bromide (MTT) assay system.

RESULTS:

The overall survival rate was significantly higher in 25 cases of lower CYP24 expression than 17 cases of higher CYP24 expression (P <0.05); on the other hand, 23 cases of low VDR expression had a poorer prognosis than 19 cases of high VDR expression. Moreover, we disclosed that the inverse correlation between CYP24 and VDR expression is significant in esophageal cancer cases (P <0.05). Furthermore, the cell growth evaluated by MTT assay was greatly increased in CYP24-induced and VDR-diminished cells than non-responding cells by 25(OH)D3 activity (P <0.01).

CONCLUSIONS:

Overexpression of the candidate oncogene CYP24 is inversely correlated to vitamin D receptor expression, and may play an important role in determination of the malignant potential of esophageal cancer.

• Authors: K Mimori, Y Tanaka, K Yoshinaga, T Masuda, K Yamashita, M Okamoto, H Inoue, M Mori
• Journal: Annals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 15 Issue 2 Pg. 236-41 (Feb 2004) ISSN: 0923-7534 [Print] England
• PMID: 14760115 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Receptors, Calcitriol
• Cytochrome P-450 Enzyme System
• Steroid Hydroxylases
• Vitamin D3 24-Hydroxylase

Topics

• Adult
• Aged
• Aged, 80 and over
• Cytochrome P-450 Enzyme System (biosynthesis, pharmacology)
• Esophageal Neoplasms (genetics, pathology)
• Female
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Humans
• Male
• Middle Aged
• Prognosis
• Receptors, Calcitriol (biosynthesis, genetics)
• Reverse Transcriptase Polymerase Chain Reaction
• Steroid Hydroxylases (biosynthesis, pharmacology)
• Survival Analysis
• Tumor Cells, Cultured
• Vitamin D3 24-Hydroxylase