Abstract A13: Constitutively-active HRAS suppresses stochastic Erk activity pulses in Madin-Darby canine kidney cells

Abstract

The EGFR-Ras-ERK pathway is a major growth signaling cascade in many human cancers. Consequently, constitutive activation of Ras, which is found in 30% of human cancers, is believed to lead to constitutive ERK activation and, thereby, uncontrolled cell growth. Recently, we have reported that the cell growth is controlled not only by the basal ERK activity but also by the frequency of stochastic ERK activity pulses. In the present study, we have evaluated the effect of Ras on the temporal dynamics of Erk activity by using fluorescent resonance energy transfer (FRET) biosensors. We found that, in Madin-Darby Canine kidney (MDCK) cells expressing constitutively active HRAS (HRASV12), ERK activity stimulated by epidermal growth factor (EGF) and 12-O-tetradecanoylphorbol-13-acetate (TPA), was markedly attenuated in comparison with the parent MDCK cells. Furthermore, the stochastic ERK activity pulses observed in the parent MDCK cells were almost completely abolished in the HRASV12-expressing MDCK cells. These observations have revealed that the temporal regulation of ERK activity is significantly different between normal and HRASV12-expressing cells. Citation Format: Noriyuki Kawabata, Michiyuki Matsuda. Constitutively-active HRAS suppresses stochastic Erk activity pulses in Madin-Darby canine kidney cells. [abstract]. In: Proceedings of the AACR Special Conference on RAS Oncogenes: From Biology to Therapy; Feb 24-27, 2014; Lake Buena Vista, FL. Philadelphia (PA): AACR; Mol Cancer Res 2014;12(12 Suppl):Abstract nr A13. doi: 10.1158/1557-3125.RASONC14-A13