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


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.
Mimori
K
K
Department of Surgery, Medical Institute of Bioregulation, Kyushu University, Beppu, Japan.
Tanaka
Y
Y
Yoshinaga
K
K
Masuda
T
T
Yamashita
K
K
Okamoto
M
M
Inoue
H
H
Mori
M
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000494:pharmacology*; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D018167:Receptors, Calcitriol / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013250:Steroid Hydroxylases / Q000096:biosynthesis* / Q000494:pharmacology*; D016019:Survival Analysis; D014407:Tumor Cells, Cultured; D065668:Vitamin D3 24-Hydroxylase
D018167:Receptors, Calcitriol; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D065668:Vitamin D3 24-Hydroxylase