¹Max Planck Institute for Physiological and Clinical Research, Department of Molecular Cell Biology, 61231 Bad Nauheim, Germany

Correspondence: Hennes CA Drexler, Department of Molecular Cell Biology, Max Planck Institute for Physiological and Clinical Research, Parkstr. 1, 61231 Bad Nauheim, Germany. Tel: +49 6032 705296; Fax:+49 6032 72259; E-mail: h.drexler@kerckhoff.mpg.de

Received 27 March 2002; Revised 17 September 2002; Accepted 30 September 2002.

Abstract

Overexpression of the cyclin-dependent kinase inhibitor p27^Kip1 has been demonstrated to induce cell cycle arrest and apoptosis in various cancer cell lines, but has also been associated with the opposite effect of enhanced survival of tumor cells and increased resistance towards chemotherapeutic treatment. To address the question of how p27^Kip1 expression is related to apoptosis induction, we studied doxycycline-regulated p27^Kip1 expression in K562 erythroleukemia cells. p27^Kip1 expression effectively retards proliferation, but it is not sufficient to induce apoptosis in K562 cells. p27^Kip1-expressing K562 cells, however, become resistant to apoptosis induction by the proteasome inhibitors PSI, MG132 and epoxomicin, in contrast to wild-type K562 cells that are efficiently killed. Cell cycle arrest in the S phase by aphidicolin, which is not associated with an accumulation of p27^Kip1 protein, did not protect K562 cells against the cytotoxic effect of the proteasome inhibitor PSI. The expression levels of p27^Kip1 thus constitute an important parameter, which decides on the overall sensitivity of cells against the cytotoxic effect of proteasome inhibitors.