title: H-ras up-regulates expression of BNIP3.
abstract: BACKGROUND
  Bcl-2/adenovirus E1B 19-kDa protein-interacting protein 3 (BNIP3) is a key regulator of cell death/autophagy and can act as an effector of a necrosis-like, atypical death program. It was implicated in execution of cell death induced by cluster of differentiation 47 (CD47). Despite the postulated role of BNIP3 in the regulation of survival of cancer cells, the influence of oncogenic transformation on BNIP3 expression is unclear.
  
  
  METHODS
  The influence of oncogenic transformation on expression of BNIP3 was studied using H-ras-transformed cells. The consequences of BNIP3 expression for sensitivity to CD47-mediated cell death were assessed using tetrazolium salt-based assay.
  
  
  RESULTS
  Here, the enforced and endogenous expression of Ras coincided with the up-regulation of BNIP3 across a wide spectrum of cancer cells, providing the first experimental evidence that BNIP3 is a regulatory target of H-Ras. This indicated that merely the introduction of a single oncogene may result in the up-regulation of BNIP3. The consequences of CD47 ligation strongly depended on the BNIP3 presence, which in turn correlated with Ras expression. Interestingly, the indirect effect of that phenomenon was the selective sensitivity of Ras-transformed cells to CD47-mediated cell death.
authors.affiliation: Department of Experimental Oncology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland. kalas@iitd.pan.wroc.pl
authors.forename: Wojciech
authors.initials: W
authors.lastname: Kalas
authors.forename: Ewelina
authors.initials: E
authors.lastname: Swiderek
authors.forename: Andrzej
authors.initials: A
authors.lastname: Rapak
authors.forename: Magdalena
authors.initials: M
authors.lastname: Kopij
authors.forename: Janusz
authors.initials: J
authors.lastname: Rak
authors.forename: Leon
authors.initials: L
authors.lastname: Strzadala
mesh_terms: D000818:Animals; D002461:Cell Line, Transformed; D011905:Genes, ras; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics*
chemical_list: C090121:BNIP3 protein, human; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins