Vitamin D3 receptor expression in N-ethylnitrosourea-induced mouse pulmonary adenomas.
Vitamin D3 receptor expression in N-ethylnitrosourea-induced mouse pulmonary adenomas.
复制标题
N-乙基亚硝基脲诱导的小鼠肺腺瘤中维生素 D3 受体的表达。
DOI：
10.1165/ajrcmb.11.4.7917316
复制
发表时间：
1994
影响因子：
6.4
通讯作者：
Palmer,KC
中科院分区：
文献类型：
--
作者：
Zhong,K;Chua,BH;Palmer,KC
最近的证据表明，维生素D（1 α，25-（OH）2D 3）在哺乳动物系统中的作用扩大，其受体（维生素D受体[VDR]）不仅存在于经典的靶器官中，而且存在于各种正常组织和器官、肿瘤组织和癌细胞系中。维生素D不仅参与钙稳态和骨代谢的调节，还参与细胞增殖、分化和免疫反应的调节。维生素D在正常肺生长、发育和维持中的作用尚不清楚。同样，它在肺肿瘤发生中的作用也不清楚。本研究检测了VDR结合活性和VDR在正常小鼠肺和乙基亚硝基脲诱导的肺腺瘤中的表达。1 α，25-（OH）2D 3的结合在0.01至0.50 nM的浓度范围内具有特异性和饱和性，亲和力（Kd）为0.93 x 10（-10）M，总结合容量（Bmax）为22 fmol/mg蛋白质。Scatchard分析产生了一个凸曲线，这表明正受体协同性。在0.4 nM的受体浓度下，计算的希尔系数等于1.69，与受体的二聚化一致。Western blot分析显示肿瘤组织匀浆中存在60 kD VDR蛋白，而北方印迹分析检测到肿瘤组织制备物中存在4.4 kb VDR mRNA。免疫组化和原位杂交显示，腺瘤性Clara细胞和正常细支气管上皮Clara细胞表达VDR，其受体蛋白存在于细胞核中。（250字处删节）
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)