Cyclic AMP, the microtubule-microfilament system, and cancer.

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Abstract
Additional evidence is presented for the previously proposed existence in normal fibroblasts of a cyclic[c] AMP-dependent network of microtubules and microfilaments, which is connected with cell membrane elements on 1 end and nuclear structures on the other, and whose disorganization leads to malignant transformation. In the presence of cAMP derivatives sufficient to promote integrity of this network, cell growth limitation in suspension, increased transport of .alpha.-[14C]aminobutyrate and the relatively tranquilized membrane of the normal fibroblast are also achieved. A pattern of distribution of actin and tubulin was demonstrated showing aggregated actin deposits which are presumably responsible for the oscillatory knob activity of cells with the transformed habitus. Specific orientations of microtubular and filamentous elements with respect to the nucleus can be demonstrated. The hypothesis that the microtubular-microfilamentous structure conveys growth-regulatory information from the cell membrane to the nucleus and its disorganization can lead to malignancy was extended to explain various cellular manifestations in chinese hamster ovary cells.