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Annals of Oncology 15:236-241, 2004
© 2004 European Society for Medical Oncology

Original Paper

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

Received 16 January 2003; revised 25 August 2003; accepted 29 September 2003;

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.

K. Mimori1, Y. Tanaka2, K. Yoshinaga1, T. Masuda1, K. Yamashita1, M. Okamoto1, H. Inoue1 and M. Mori1,*

1 Department of Surgery, Medical Institute of Bioregulation, Kyushu University, Beppu; 2 Department of Surgery, Saitama Cancer Center, Saitama, Japan

Key words: 20q13.2, esophageal cancer, oncogene, prognostic factor, vitamin D 24-hydroxylase, vitamin D receptor


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