HETEROGENEITY OF HUMAN RENAL CELL CARCINOMA

III: 1α, 25-Dihydroxyvitamin D₃ Receptor and Inhibition on the Growth of Renal Carcinoma Cell Lines

Abstract

Recently much attention has been focused on the receptor for 1α, 25-dihydroxyvitamin D₃ [1α, 25(OH)₂D₃], which is an active form of vitamin D₃, in cancer cells and on growth-inhibitory effects by 1α, 25(OH)₂D₃. In the present study, we examined the presence of receptors for 1α, 25(OH)₂D₃ and the sensitivity to 1α, 25(OH)₂D₃ of renal carcinoma cell line KU-2 and its 4 clones as a cumulative study for heterogeneity of human renal cell carcinoma.
Radioreceptor assay and sucrose density gradient analysis showed that all of the clones have 3.2S cytosolic receptor proteins with high affinity (Kd=20-30nM) which was the same as the receptor in normal kidneys. Binding capacity of the receptors in KU-2, N-7, N-8, N-10 and N-13 was 87, 69, 57, 60 and 106fmol/mg protein, respectively. Of these clones, N-13 is thought to be the most differentiated because of its high receptor capacity together with morphological features and poor tumorigenicity. 1α, 25(OH)₂D₃ dose-dependently suppressed proliferation of these clones in a monolayer culture and also suppressed their clonogenicity in a soft agar culture. N-8 was relatively resistant to the inhibitory effect of 1α, 25(OH)₂D₃, although its receptor capacity was similar to that of N-7 or N-10. In other clones, the growth suppression by 1α, 25(OH)₂D₃ was correlated with the amount of receptor binding sites in each clone. These indicate that the effect of 1α, 25(OH)₂D₃ in inhibiting proliferation and clonogenicity are affected by the receptor capacity of the target cells.
Although the clone cells are genetically very closed, the results indicate that KU-2 consists of cells heterogeneous in sensitivity to the bioeffects by 1α, 25(OH)₂D₃ and in amount of 1α, 25(OH)₂D₃ receptors. Also these clones may propose useful informations in analysis of the role of 1α, 25(OH)₂D₃ and its receptor in renal carcinoma cells.