The candidate oncogene CYP24A1: A potential biomarker for colorectal tumorigenesis.
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.
Horváth
Henrik C
HC
Department of Medicine, Semmelweis University, Budapest, Hungary.
Lakatos
Péter
P
Kósa
János P
JP
Bácsi
Krisztián
K
Borka
Katalin
K
Bises
Giovanna
G
Nittke
Thomas
T
Hershberger
Pamela A
PA
Speer
Gábor
G
Kállay
Enikö
E
D000230:Adenocarcinoma / Q000201:enzymology* / Q000473:pathology; D000236:Adenoma / Q000201:enzymology* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D049109:Cell Proliferation; D003106:Colon / Q000201:enzymology; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000201:enzymology; D019394:Ki-67 Antigen / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000096:biosynthesis; D018167:Receptors, Calcitriol / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013250:Steroid Hydroxylases / Q000096:biosynthesis* / Q000235:genetics; D065668:Vitamin D3 24-Hydroxylase
D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D012333:RNA, Messenger; D018167:Receptors, Calcitriol; D013250:Steroid Hydroxylases; C585549:CYP24A1 protein, human; D065668:Vitamin D3 24-Hydroxylase