Time correlation of commitment to calcium-induced apoptosis and terminal differentiation in human ectocervical...

The terminal differentiation of epithelial keratinocytes has been proposed to be a specialized form of programmed cell death (apoptosis). We examined the time correlation of apoptosis and terminal differentiation by human ectocervical keratinocytes in a suspension culture that induces either of these events in epithelial cells. We found that a loss of cell anchorage did not result in the immediate onset of apoptotic DNA degradation but sensitized the cells to that triggered by calcium. This susceptibility appeared in parallel with the irreversible loss of growth potential and the accumulation of involucrin, suggesting that the ectocervical keratinocytes in suspension become competent to calcium-inducible apoptosis as they committed to terminal differentiation. Cycloheximide, which inhibited the calcium induction of DNA fragmentation, was also inhibitory to terminal differentiation. These correlations support the notion that terminal differentiation of keratinocytes couples with apoptosis. Apoptosis seemed to be independent of p53 because it was down-regulated in suspension cultures of ectocervical keratinocytes.