PMID: 7547502Jul 1, 1995Paper

A secreted serine protease can induce apoptosis in Pam212 keratinocytes

Cell Growth & Differentiation : the Molecular Biology Journal of the American Association for Cancer Research
J MarthinussM Seiberg

Abstract

The epidermal keratinocyte cell line Pam212 undergoes spontaneous apoptosis in culture, providing an in vitro model for the early steps of epidermal differentiation. Pam212 cells exhibit characteristics of basal keratinocytes, committed for the transition to the spinous layer of the epidermis. Bcl-2 can regulate the differentiation of these cells by negatively regulating several genes that have been implicated in apoptosis. We show evidence that a serine protease activity, secreted by the Pam212 cells, could induce apoptosis in Pam212 and several other cell lines. This activity might be regulated via the bcl-2 pathway. We suggest that this serine protease could either directly, via binding and/or cleavage of a serine protease-activated receptor, or indirectly, via the cleavage of an unknown protein, activate the signaling for apoptosis in Pam212 cells. Alternatively, this secreted serine protease could reenter the cell and start a proteolytic cascade reaction that leads to cell death. This is based on the induction of apoptosis in several cell lines by the partially purified serine protease activity, and the minimal effect of protein synthesis inhibition on Pam212 apoptosis. We propose that in vivo, a two-step mechanism control...Continue Reading

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