The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

Håkan Axelson

Håkan Axelson

Research team manager

Håkan Axelson

Simultaneous targeted activation of Notch1 and Vhl-disruption in the kidney proximal epithelial tubular cells in mice

Author

  • Elinn Johansson
  • Birgitte Rönö
  • Martin Johansson
  • David Lindgren
  • Christina Möller
  • Håkan Axelson
  • Emma M K Smith

Summary, in English

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancer, representing approximately 75% of all renal neoplasms. ccRCC is known to be strongly associated with silencing of the von Hippel Lindau (VHL) tumor suppressor gene, yet VHL deficiency alone does not seem to be sufficient to drive the oncogenic transformation of normal renal epithelium and induce renal tumorigenesis. We, and others, have previously suggested that constitutive activation of the Notch signaling pathway, alongside with VHL loss, contribute to the oncogenic features of ccRCC. Here we report a prevailing hyperactivation of the Notch1 receptor in human ccRCC relative to the healthy counterpart. To explore the consequences of the elevated Notch1 signaling observed in ccRCC patient material, we made use of a conditional mouse model based on concurrent ectopic expression of constitutively active Notch1 (NICD1) and deletion of the Vhl gene. Histological examination of the kidneys of the conditional mice demonstrate the existence of nests of dysplastic cells with a clear cytoplasm as a consequence of lipid accumulation, thus displaying a one important hallmark of human ccRCC.

Department/s

  • Kidney cancer research group
  • Division of Translational Cancer Research
  • Department of Translational Medicine
  • Clinical pathology, Malmö
  • BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
  • Division of Molecular Hematology (DMH)

Publishing year

2016-08-06

Language

English

Publication/Series

Scientific Reports

Volume

6

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Cancer and Oncology
  • Medical Genetics

Status

Published

Research group

  • Kidney cancer research group
  • Clinical pathology, Malmö

ISBN/ISSN/Other

  • ISSN: 2045-2322