Contact-inhibition-induced quiescent state is marked by intense nuclear expression of statin

Statin, a nuclear protein of 57,000 daltons, is found in in vitro aged, nonproliferating human fibroblasts but not in their young, replicating counterparts or transformed derivatives; it is also found in the nuclei of young fibroblasts when their growth is arrested but rapidly disappears from the cells once the restriction to growth is removed. We reported earlier that as cells leave the quiescent state, the loss of statin from the nucleus precedes the initiation of DNA synthesis; here we report that in a confluent culture, as cells leave the traverse of the replicative cycle and assume the quiescent phenotype, statin is not expressed maximally until total contact inhibition of growth is achieved. This full manifestation of statin occurs in monolayer culture with cells forming the typical swirling pattern and fibronectin organized into large intercellular cables. The late expression of statin in cells approaching the quiescent state is also verified biochemically by immunoblotting assays. The present results, taken together with those reported earlier, indicate that the nuclear appearance of statin occurs only after the complete cessation of DNA synthesis and that the full manifestation of this protein can be used as a marker for the G0 quiescent state.