Calcium-Activatable Phosphodiesterase and Calcium-Dependent Modulator Protein in Transplantable Hepatoma Tissues

Abstract

The activities of cyclic nucleotide phosphodiesterase [EC 3.1.4.17] and levels of Ca²⁺-dependent modulator protein in rapidly growing (3924A) and slowly growing (9633 and 7794A) Morris hepatomas were compared with those in normal or host liver. Hydrolysis of cyclic GMP in the supernatants of tumor homogenates was more stimulated than that in supernatants of normal liver homogenates by Ca²⁺ and modulator protein: 3.39-fold (3924A), 2.20-fold (9633), and 1.26-fold (normal liver) stimulations were seen. Ca²⁺-activatable phosphodiesterase, which has been found in a variety of nontumor tissues, was identified in extracts of hepatomas by gel filtration chromatography. The greater effect of Ca²⁺ and modulator protein on tumor extracts was due to elevated levels of this enzyme with concomitant reductions in the levels of other types of phosphodiesterase in the hepatoma extracts. 3924A showed a greater change in isozyme pattern than 9633 or 7794A. The concentrations of modulator protein in the soluble fraction from hepatomas were about 2.6 times (3924A) and 1.4 times (9633) that in the same fraction from normal liver. However, its concentrations in the particulate fraction of the hepatomas were about one-fifth (3924A) and one-half (9633) of that in the same fraction of normal liver. Consequently, the sums of the amounts of modulator protein in the two fractions of tumors were similar to that in normal liver. It is suggested that the Ca²⁺/modulator protein system may be involved in the control of cell proliferation.