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The transcription factor RUNX2 regulates receptor tyrosine kinase expression in melanoma.
Boregowda, Rajeev K; Medina, Daniel J; Markert, Elke; Bryan, Michael A; Chen, Wenjin; Chen, Suzie; Rabkin, Anna; Vido, Michael J; Gunderson, Samuel I; Chekmareva, Marina; Foran, David J; Lasfar, Ahmed; Goydos, James S; Cohen-Solal, Karine A.
Afiliación
  • Boregowda RK; Division of Medical Oncology, Department of Medicine, Robert Wood Johnson Medical School, Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ 08903, USA.
  • Medina DJ; Division of Medical Oncology, Department of Medicine, Robert Wood Johnson Medical School, Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ 08903, USA.
  • Markert E; Cancer Research UK Beatson Institute, Glasgow, G61 1BD Scotland, UK.
  • Bryan MA; Division of Medical Oncology, Department of Medicine, Robert Wood Johnson Medical School, Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ 08903, USA.
  • Chen W; Center for Biomedical Imaging & Informatics, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA.
  • Chen S; Department of Pathology and Laboratory Medicine, Robert Wood Johnson University Hospital, Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901, USA.
  • Rabkin A; Department of Chemical Biology, Susan Lehman Cullman Laboratory for Cancer Research, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, New Brunswick, NJ 08903, USA.
  • Vido MJ; Department of Chemical Biology, Susan Lehman Cullman Laboratory for Cancer Research, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, New Brunswick, NJ 08903, USA.
  • Gunderson SI; Department of Cancer Biology and Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.
  • Chekmareva M; Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ 08854, USA.
  • Foran DJ; Department of Pathology and Laboratory Medicine, Robert Wood Johnson University Hospital, Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901, USA.
  • Lasfar A; Center for Biomedical Imaging & Informatics, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA.
  • Goydos JS; Department of Pathology and Laboratory Medicine, Robert Wood Johnson University Hospital, Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901, USA.
  • Cohen-Solal KA; Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
Oncotarget ; 7(20): 29689-707, 2016 May 17.
Article en En | MEDLINE | ID: mdl-27102439
Receptor tyrosine kinases-based autocrine loops largely contribute to activate the MAPK and PI3K/AKT pathways in melanoma. However, the molecular mechanisms involved in generating these autocrine loops are still largely unknown. In the present study, we examine the role of the transcription factor RUNX2 in the regulation of receptor tyrosine kinase (RTK) expression in melanoma. We have demonstrated that RUNX2-deficient melanoma cells display a significant decrease in three receptor tyrosine kinases, EGFR, IGF-1R and PDGFRß. In addition, we found co-expression of RUNX2 and another RTK, AXL, in both melanoma cells and melanoma patient samples. We observed a decrease in phosphoAKT2 (S474) and phosphoAKT (T308) levels when RUNX2 knock down resulted in significant RTK down regulation. Finally, we showed a dramatic up regulation of RUNX2 expression with concomitant up-regulation of EGFR, IGF-1R and AXL in melanoma cells resistant to the BRAF V600E inhibitor PLX4720. Taken together, our results strongly suggest that RUNX2 might be a key player in RTK-based autocrine loops and a mediator of resistance to BRAF V600E inhibitors involving RTK up regulation in melanoma.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Regulación Neoplásica de la Expresión Génica / Proteínas Tirosina Quinasas Receptoras / Comunicación Autocrina / Subunidad alfa 1 del Factor de Unión al Sitio Principal / Melanoma Límite: Humans Idioma: En Revista: Oncotarget Año: 2016 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Regulación Neoplásica de la Expresión Génica / Proteínas Tirosina Quinasas Receptoras / Comunicación Autocrina / Subunidad alfa 1 del Factor de Unión al Sitio Principal / Melanoma Límite: Humans Idioma: En Revista: Oncotarget Año: 2016 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos