Role of p90(rsk) in Breast Cancer Cell Survival From Apoptosis

摘要

Evidence suggests that sensitivity to chemotherapy is largely due to a functional apoptotic pathway. Thus, a better understanding of the signal transduction pathways that lead to rescue from apoptosis might lead to improved modalities of treatment for unresponsive cancer types. The focus of our studies is to elucidate the role of p90 in antagonizing apoptosis in breast cancer cells. P90 is a serine-threonine protein kinase in the Ras-Raf-ERK (extracellular signal-regulated kinase, also known as mitogen-activated protein kinase or MAP kinase) cascade that lies immediately downstream of ERK1/2. Although the Ras pathway and ERKs have been the focus of much research in the cancer field, less is known about the role of p90(rsk). We hypothesize that p90(rsk) may be particularly relevant to breast cancer cell survival because evidence suggests it can not only directly phosphorylate and activate the estrogen receptor but also has the potential to antagonize apoptosis by phosphorylating and inactivating Bad, a proapoptotc Bcl family member. In these studies, we tested the hypothesis that p90(rsk) may also have the ability to phosphorylate and inactivate the forkhead family of transcription factors, such as FKHRL1. Our preliminary result, presented here, suggest this may indeed be the case.