TIME-CORRELATION OF COMMITMENT TO CALCIUM-INDUCED APOPTOSIS AND TERMINAL DIFFERENTIATION IN HUMAN ECTOCERVICAL KERATINOCYTES IN SUSPENSION-CULTURES

The terminal differentiation of epithelial keratinocytes has been prop osed to be a specialized form of programmed cell death (apoptosis). We examined the time correlation of apoptosis and terminal differentiati on by human ectocervical keratinocytes in a suspension culture that in duces 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 o f growth potential and the accumulation of involucrin, suggesting that the ectocervical keratinocytes in suspension become competent to calc ium-inducible apoptosis as they committed to terminal differentiation, Cycloheximide, which inhibited the calcium induction of DNA fragmenta tion, was also inhibitory to terminal differentiation. These correlati ons support the notion that terminal differentiation of keratinocytes couples with apoptosis. Apoptosis seemed to be independent of p53 beca use it was down-regulated in suspension cultures of ectocervical kerat inocytes.