Novel anti-apoptotic effect of the retinoblastoma protein: implications for polyamine analogue toxicity

Abstract

The retinoblastoma protein (pRb) pathway is frequently altered in breast cancer cells. pRb is involved in the regulation of cell proliferation and cell death. The breast cancer cell line L56Br-C1 does not express pRb and is extremely sensitive to treatment with the polyamine analogue N(1),N(11)-diethylnorspermine (DENSPM) which causes apoptosis. Polyamines are essential for the regulation of cell proliferation, cell differentiation and cell death. DENSPM depletes cells of polyamines, e.g., by inducing the activity of the polyamine catabolic enzyme spermidine/spermine N(1)-acetyltransferase (SSAT). In this study, L56Br-C1 cells were transfected with human pRb-cDNA. Overexpression of pRb inhibited DENSPM-induced cell death and DENSPM-induced SSAT activity. This suggests that the pRb protein level is a promising marker for polyamine depletion sensitivity and that there is a connection between pRb and the regulation of SSAT activity. We also show that SSAT protein levels and SSAT activity do not always correlate, suggesting that there is an unknown regulation of SSAT.

Role of polyamines, their analogs and transglutaminases in biological and clinical perspectives

“…Treatment with the polyamine analogue N 1 ,N 11 diethylnorspermine (DENSPM) causes apoptosis in L56Br-C1 (Hegardt et al 2002). Now, Johansson et al (2011) show that overexpression of pRb rescues DENSPM-treated L56Br-C1 cells while lowering the activity of the polyamine catabolic enzyme SSAT. This suggests that the pRb protein may be a marker for polyamine depletion sensitivity and that there is a connection between pRb and the regulation of SSAT activity.…”