Menu

Javascript is not activated in your browser. This website needs javascript activated to work properly.
You are here

HIF-2α Expression Is Suppressed in SCLC Cells, Which Survive in Moderate and Severe Hypoxia When HIF-1α Is Repressed.

Author:
  • Matilda Munksgaard Persson
  • Martin Johansson
  • Nastaran Monsef
  • Maria Planck
  • Siv Beckman
  • Michael J Seckl
  • Lars Rönnstrand
  • Sven Påhlman
  • Helen Pettersson
Publishing year: 2012
Language: English
Pages: 494-504
Publication/Series: American Journal of Pathology
Volume: 180
Issue: 2
Document type: Journal article
Publisher: American Society for Investigative Pathology

Abstract english

Small cell lung carcinoma (SCLC) is extremely aggressive and frequently metastasizes widely in its early stage. Because tumor hypoxia is related to aggressive tumor behavior and the hypoxic adaptation of SCLC is poorly documented, we stained SCLC tumors arranged in a tissue microarray for hypoxia-inducible factor (HIF)-1α and HIF-2α proteins. We found an overall lack of HIF-2α protein expression, which was confirmed in large tumor sections. HIF-1α protein was strongly expressed in most tumors, frequently adjacent to necrotic regions. In concordance, cultured SCLC but not non-small cell lung carcinoma cells showed no or extremely low levels of HIF-2α mRNA and no HIF-2α protein at hypoxia. HIF-1α was stabilized after 4 hours at hypoxia, and its accumulation increased up to 96 hours. SCLC cells survived well and showed net proliferation and low cell death in modest (1% oxygen) and severe (0.1% oxygen) hypoxia. HIF-1α repression virtually did not influence cell death or viability despite reduced levels of hypoxia-inducible genes, such as BNIP3 and BNIP3L. At 1% oxygen no increased autophagy (LC3B-II activation) or NF-κB signaling were detected, whereas the unfolded protein response was activated at severe hypoxia. Our data indicate that HIFs are not exclusively required for SCLC cell survival at modest or severe hypoxia and that additional, yet uncharacterized, hypoxia-driven adaptation pathways may become activated.

Keywords

  • Cell and Molecular Biology

Other

Published
  • Pathology, Malmö
  • Research Group Lung Cancer
  • ISSN: 1525-2191
Sven Påhlman
E-mail: sven.pahlman [at] med.lu.se

Professor

Division of Translational Cancer Research

+46 46 222 64 21

MV406 312K1

90