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Increased Expression of the 25-Hydroxyvitamin D₃-1-Hydroxylase Gene in Alveolar Macrophages of Patients with Lung Cancer

Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan

Address all correspondence and requests for reprints to: Hirotoshi Nakamura, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu 431-3192, Japan. E-mail: hirotosh{at}hama-med.ac.jp.

25-Hydroxyvitamin D₃-1-hydroxylase (1-hydroxylase) plays a central role in calcium metabolism by synthesizing the active hormone 1,25-dihydroxyvitamin D₃ 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 1-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 1-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 1-hydroxylase-mRNA level was well correlated with serum 1,25-dihydroxylase D₃ concentration and the 1,25-dihydroxylase D₃ to 25-hydroxyvitamin D₃ ratio, but none of the findings related to calcium metabolism among the patients with lung cancer. Increased local production of 1,25-dihydroxyvitamin D₃ may be associated with the pathological conditions, such as immunosuppression, in lung cancer.

Abbreviations: AM, Alveolar macrophage; BAL, bronchoalveolar lavage; -hydroxylase, 25-hydroxyvitamin D₃-1-hydroxylase; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; IFN, interferon; 11,25-(OH)₂ D₃, 1,25-dihydroxyvitamin D₃; 25-(OH) D₃, 25-hydroxyvitamin D₃.

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