Relationship of p21(WAF1/CIP1/SDI1) to cell proliferation in primary cultures of adrenocortical cells.

p21(WAF1/CIP1/SDI1) was originally described as a protein expressed at high levels in senescent human fibroblasts. We have studied the expression of p21 in adrenocortical cells, p21 is not expressed under most circumstances in the intact adrenal gland in vivo, except when the gland is damaged. When human and bovine adrenocortical cells are isolated and placed in both short-term and long-term culture, p21 levels are much higher. These levels did not show a large increase when the cells senesce after long-term proliferation. Thus, these observations raise the question of whether the elevated p21 in primary cultures of adrenocortical cells is caused by damage or whether p21 is elevated because the cells are dividing rather than quiescent, because it has been reported that p21 levels peak in G1 and G2 in dividing cells. In the present experiments on bovine and human adrenocortical cells in primary culture, labeling techniques that correlated nuclear p21 with measures of cell proliferation (bromodeoxyuridine incorporation and nuclear Ki-67 antigen) supported the hypothesis that p21 is associated with cell division and not with damage. This is consistent with recent data showing that, when adrenocortical cells are transplanted into immunodeficient mice, p21 is associated with healthy dividing cells in the transplant, p21 is not a unique marker for senescence, and more studies are required both to clarify its role in cell biology and to determine molecular features which characterize the senescent state of cells both in vitro and in vivo.