1. Major contribution of MEK1 to the activation of ERK1/ERK2 and to the growth of LS174T colon carcinoma cells
- Author
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Jessica Shama, Jacques Pouysségur, Raquel Garcia-Medina, Emmanuel Vial, Institut de signalisation, biologie du développement et cancer (ISBDC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)
- Subjects
MESH: Carcinoma ,Male ,MAPK/ERK pathway ,MAP Kinase Kinase 1 ,environment and public health ,Biochemistry ,Small hairpin RNA ,Mice ,0302 clinical medicine ,Blood serum ,MESH: RNA, Small Interfering ,MESH: Animals ,RNA, Small Interfering ,Mitogen-Activated Protein Kinase 1 ,0303 health sciences ,Mitogen-Activated Protein Kinase 3 ,Cell biology ,030220 oncology & carcinogenesis ,Colonic Neoplasms ,embryonic structures ,MESH: MAP Kinase Kinase 1 ,biological phenomena, cell phenomena, and immunity ,MESH: Mitogen-Activated Protein Kinase 3 ,MESH: Mitogen-Activated Protein Kinase 1 ,MESH: Enzyme Activation ,MESH: Cell Line, Tumor ,Transplantation, Heterologous ,Biophysics ,Mice, Nude ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Biology ,03 medical and health sciences ,Enzyme activator ,In vivo ,MESH: Cell Proliferation ,Cell Line, Tumor ,MESH: Mice, Nude ,Animals ,Humans ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,MESH: Transplantation, Heterologous ,MESH: Mice ,Molecular Biology ,Cell Proliferation ,030304 developmental biology ,MESH: Colonic Neoplasms ,MESH: Humans ,Activator (genetics) ,Cell growth ,Carcinoma ,Cell Biology ,Molecular biology ,MESH: Male ,Enzyme Activation ,Cell culture - Abstract
Mammalian cells express two closely related MEK isoforms, MEK1 and MEK2, upstream of the ERK1/ERK2 MAPK module. Although genetic studies have suggested that MEK1 and MEK2 do not have overlapping functions in vivo, little is known about their specific contribution to the activation of ERKs and to tumor cell proliferation. We used Tet-inducible shRNA to investigate the independent role of MEK1 and MEK2 for the oncogenic and the serum-induced activation of ERK1 and ERK2 in LS174T colon carcinoma cells. We show that MEK1 is the main activator of both ERK1 and ERK2. MEK2 removal has no impact by itself but it can cooperate with MEK1 ablation for the inhibition of ERK1/2 activity. In addition, we show that MEK1 is the critical isoform regulating tumor cell proliferation in vitro and in vivo.
- Published
- 2008
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