HIF-2α Expression Is Suppressed in SCLC Cells, Which Survive in Moderate and Severe Hypoxia When HIF-1α Is Repressed.
Persson, Matilda Munksgaard ; Johansson, Martin LU ; Monsef, Nastaran ; Planck, Maria LU ; Beckman, Siv LU ; Seckl, Michael J ; Rönnstrand, Lars LU
; Påhlman, Sven
LU
and Pettersson, Helen
LU
(2012)
In American Journal of Pathology
180(2).
p.494-504
- Abstract
- 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... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2220355
- author
- Persson, Matilda Munksgaard
; Johansson, Martin
LU
; Monsef, Nastaran
; Planck, Maria
LU
; Beckman, Siv
LU
; Seckl, Michael J
; Rönnstrand, Lars
LU
; Påhlman, Sven
LU
and Pettersson, Helen
LU
- organization
- publishing date
- 2012
- type
- Contribution to journal
- publication status
- published
- subject
- in
- American Journal of Pathology
- volume
- 180
- issue
- 2
- pages
- 494 - 504
- publisher
- American Society for Investigative Pathology
- external identifiers
-
- wos:000299918800007
- pmid:22115707
- scopus:84855998771
- pmid:22115707
- ISSN
- 1525-2191
- DOI
- 10.1016/j.ajpath.2011.10.014
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Oncology, MV (013035000), Pathology (Malmö) (013031000), Experimental Clinical Chemistry (013016010), Molecular Medicine (013031200)
- id
- 467bd5ea-eef3-4e32-89c3-5a2399a582f4 (old id 2220355)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/22115707?dopt=Abstract
- date added to LUP
- 2016-04-01 11:05:25
- date last changed
- 2023-01-25 22:30:05
@article{467bd5ea-eef3-4e32-89c3-5a2399a582f4,
abstract = {{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.}},
author = {{Persson, Matilda Munksgaard and Johansson, Martin and Monsef, Nastaran and Planck, Maria and Beckman, Siv and Seckl, Michael J and Rönnstrand, Lars and Påhlman, Sven and Pettersson, Helen}},
issn = {{1525-2191}},
language = {{eng}},
number = {{2}},
pages = {{494--504}},
publisher = {{American Society for Investigative Pathology}},
series = {{American Journal of Pathology}},
title = {{HIF-2α Expression Is Suppressed in SCLC Cells, Which Survive in Moderate and Severe Hypoxia When HIF-1α Is Repressed.}},
url = {{https://lup.lub.lu.se/search/files/2370135/2365825.pdf}},
doi = {{10.1016/j.ajpath.2011.10.014}},
volume = {{180}},
year = {{2012}},
}