Kikuchi K, Tsutsumi K, Ohta Y, Yasumoto S
Laboratory of Molecular Cell Biology, Kanagawa Cancer Center Research Institute, Yokohama, Japan.
Cell Growth Differ. 1997 May;8(5):571-9.
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.
上皮角质形成细胞的终末分化被认为是一种特殊形式的程序性细胞死亡（凋亡）。我们通过悬浮培养的人宫颈外角质形成细胞来研究凋亡和终末分化的时间相关性，这种悬浮培养可诱导上皮细胞发生这两种事件中的任何一种。我们发现，细胞失去锚定并不会导致凋亡性DNA降解立即发生，但会使细胞对钙触发的凋亡敏感。这种敏感性与生长潜能的不可逆丧失和兜甲蛋白的积累同时出现，表明悬浮培养的宫颈外角质形成细胞在进入终末分化时变得对钙诱导的凋亡有反应。抑制钙诱导的DNA片段化的环己酰亚胺也抑制终末分化。这些相关性支持角质形成细胞的终末分化与凋亡相关的观点。凋亡似乎与p53无关，因为在宫颈外角质形成细胞的悬浮培养中p53表达下调。
