Increased expression of the 25-hydroxyvitamin D(3)-1alpha-hydroxylase gene in alveolar macrophages of patients with lung cancer.
25-Hydroxyvitamin D(3)-1alpha-hydroxylase (1alpha-hydroxylase) plays a central role in calcium metabolism by synthesizing the active hormone 1alpha,25-dihydroxyvitamin D(3) in the kidney. Its increased expression in the extrarenal tissues has been found in alveolar macrophages in sarcoidosis but not in any other pathological conditions. We found that 1alpha-hydroxylase-mRNA in alveolar macrophages measured by semiquantitative RT-PCR was 2-fold greater in patients with lung cancer than in control subjects (0.61 +/- 0.20 vs. 0.34 +/- 0.11, respectively; P < 0.0001). When the clinical stages of lung cancer were divided into early (stage IA-IIIA) and advanced (stage IIIB and IV) and the expression of 1alpha-hydroxylase gene was compared among the control, early, and advanced groups, the advanced group showed the highest expression, followed by the early group, then the control group (0.34 +/- 0.11, 0.52 +/- 0.11, and 0.69 +/- 0.23 for control, early, and advanced groups, respectively; P < 0.0001). The 1alpha-hydroxylase-mRNA level was well correlated with serum 1alpha,25-dihydroxylase D(3) concentration and the 1alpha,25-dihydroxylase D(3) to 25-hydroxyvitamin D(3) ratio, but none of the findings related to calcium metabolism among the patients with lung cancer. Increased local production of 1alpha,25-dihydroxyvitamin D(3) may be associated with the pathological conditions, such as immunosuppression, in lung cancer.
Yokomura
Koushi
K
Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan.
Suda
Takafumi
T
Sasaki
Shigekazu
S
Inui
Naoki
N
Chida
Kingo
K
Nakamura
Hirotoshi
H
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D002112:Calcifediol / Q000097:blood; D002118:Calcium / Q000378:metabolism; D018288:Carcinoma, Small Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D016676:Macrophages, Alveolar / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D012333:RNA, Messenger / Q000378:metabolism
D012333:RNA, Messenger; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D002112:Calcifediol; D002118:Calcium