Am. J. Respir. Cell Mol. Biol., Vol 11, No. 4, 10 1994, 480-486.
Vitamin D3 receptor expression in N-ethylnitrosourea-induced mouse pulmonary adenomas
K Zhong, BH Chua and KC Palmer
Department of Pathology, Wayne State University School of Medicine, Detroit, Michigan 48201.
An expanded role for vitamin D (1 alpha,25-(OH)2D3) in mammalian systems
has been suggested by recent evidence that its receptor (vitamin D receptor
[VDR]) is present not only in classical target organs, but in a variety of
normal tissues and organs, tumor tissues, and cancer cell lines. Vitamin D
is involved not only in the regulation of calcium homeostasis and bone
metabolism, but in the regulation of cell proliferation, differentiation,
and immune responses. The role vitamin D may play in normal lung growth,
development, and maintenance is unknown. Likewise, its part in lung
tumorigenesis is unclear. The present study examined VDR binding activity
and VDR expression in normal mouse lung and ethylnitrosourea-induced lung
adenomas. Binding of 1 alpha,25-(OH)2D3 was specific and saturable over the
concentration range of 0.01 to 0.50 nM, with an affinity (Kd) of 0.93 x
10(-10) M and a total binding capacity (Bmax) of 22 fmol/mg of protein.
Scatchard analysis yielded a convex curve, which suggests positive receptor
cooperativity. The calculated Hill coefficient equals 1.69, at a receptor
concentration of 0.4 nM, consistent with dimerization of the receptor.
Western blot analysis showed the presence of 60 kD VDR protein in tumor
homogenates, while Northern blot analysis detected the 4.4 kb VDR mRNA in
tumor tissue preparations. Immunohistochemistry and in situ hybridization
revealed that both adenomatous Clara cells and normal bronchiolar
epithelial Clara cells expressed VDR, with the receptor protein present in
their nuclei.(ABSTRACT TRUNCATED AT 250 WORDS)
