Comparison of corticoid receptor and other cytoplasmic factors among liver and hepatoma cell lines with different sensitivity to corticoid inhibition of cell growth

Abstract

1. 1. The cell lines derived from the rat liver and hepatoms were divided into two groups with respect to the glucocorticoid inhibition of cell grwoth: sensitive cells (J-5-2, Fu5) and insensitive cells (dRLa-74, AH-66, AH-130, AH-130F (N), AH-7974). The dexamethasone inhibition of Fu5 cell growth was reversible, and a half maximal inhibition was found at 2.7 nM (cell proliferation) or 1.2 nM (DNA synthesis). 2. 2. The cellular uptake of [ 3H]dexamethasone (6 · 10 −7 M) and the intracellular translocation of the [ 3H]dexamethasone into nuclei were lower in the insensitive cells (AH-130, AH-7974) as compared to the sensitive ones (Fu5). The cellular uptake of [ 3H]dexamethasone increased with hormone concentrations up to 3 · 10 −7 M, whereas the intranuclear [ 3H]dexamethasone reached a plateau at about 3 · 10 −8 M, showing a half-maximal level at about 3.5 nM. 3. 3. In the cell-free systems consisting of various nuclei and the same cytosol, the nuclear uptake of [ 3H]dexamethasone was the same among nuclei of sensitive (liver) and insensitive (AH-130, AH-7974) cells. On the other hand, the nuclear uptake of [ 3H]dexamethasone in the presence of liver cytosol was larger than that in the presence of ascites hepatoma cytosol. 4. 4. No difference was detected among the cytosols of sensitive (liver, Fu5) and insensitive (AH-130, AH-7974) cells in the dissociation constant for the receptor. [ 3H]dexamethasone complex. However, the receptor content appeared to be larger in the sensitive cells as cmpared to the insensitive cells. 5. 5. In addition to the quantitative difference in the cytosol receptor, a cytosol factor inhibiting the translocation of activated receptor · hormone complexes into nuclei as well as another cytosol factor inhibiting the activation of receptor · hormone compelxes appeared to be somewhat higher in the ascites hepatoma (AH-130, AH7974) as compared to the liver and Fu5 cells.