Human cytotrophoblast expression of the von Hippel-Lindau protein is downregulated during uterine invasion in situ and upregulated by hypoxia in vitro

Developmental Biology
O GenbacevS J Fisher

Abstract

The von Hippel-Lindau tumor-suppressor protein (pVHL) regulates the stability of HIF1 alpha and HIF2 alpha and thus is pivotal in cellular responses to changes in oxygen tension. Paradoxically, human cytotrophoblasts proliferate under hypoxic conditions comparable to those measured in the early gestation placenta (2% O(2)), but differentiate into tumorlike invasive cells under well-oxygenated conditions such as those found in the uterus. We sought to explain this phenomenon in terms of pVHL expression. In situ, pVHL immunolocalized to villous cytotrophoblast stem cells, and expression was enhanced at sites of cell column initiation; in both of these relatively hypoxic locations, cytoplasmic staining for HIF2 alpha was also detected. As cytotrophoblasts attached to and invaded the uterus, which results in their increased exposure to oxygen, pVHL staining was abruptly downregulated concordant with localization of HIF2 alpha to the nucleus. In vitro, hypoxia (2% O(2)) upregulated cytotrophoblast pVHL expression together with HIF2 alpha, which localized to the cytoplasm; culture under well-oxygenated conditions greatly reduced levels of both molecules. These results, together with the placental defects previously observed in VHL(-/...Continue Reading

References

Apr 1, 1991·The Journal of Cell Biology·C L LibrachS J Fisher
Mar 1, 1993·The Journal of Clinical Investigation·Y ZhouS J Fisher
Feb 15, 1995·JAMA : the Journal of the American Medical Association·W M LinehanB Zbar
Sep 22, 1994·Nature·F GuillemotA L Joyner
May 1, 1996·Biological Signals·G P DimriJ Campisi
Aug 19, 1997·Proceedings of the National Academy of Sciences of the United States of America·J R GnarraW M Linehan
Sep 12, 1997·Science·O GenbacevS J Fisher
Dec 17, 1997·Developmental Biology·K R KozakO Hankinson
Dec 31, 1997·Medicine·E R Maher, W G Kaelin
Mar 14, 1998·Proceedings of the National Academy of Sciences of the United States of America·A PauseR D Klausner
Nov 18, 1998·Current Opinion in Cell Biology·C H Damsky, S J Fisher
Jun 3, 1999·Nature·W G Kaelin
Aug 24, 1999·Cell·G L Semenza
May 24, 2000·The Journal of Biological Chemistry·M E CockmanP H Maxwell
Dec 22, 2000·Genes & Development·D M AdelmanE Maltepe
Apr 1, 1964·The American Journal of Medicine·K L MELMON, S W ROSEN

❮ Previous
Next ❯

Citations

Jan 17, 2002·The New England Journal of Medicine·E R NorwitzS J Fisher
Nov 21, 2009·Human Reproduction Update·K G PringleC T Roberts
Apr 14, 2006·Biology of Reproduction·Francesca IettaIsabella Caniggia
Sep 17, 2004·The Journal of Clinical Investigation·Kristy Red-HorseSusan J Fisher
May 15, 2009·Regenerative Medicine·Ana KrtolicaRichard K Miller
May 1, 2007·Regenerative Medicine·Kelly Okazaki, Emin Maltepe
Sep 22, 2012·High Altitude Medicine & Biology·Martha C Tissot van PatotAníbal J Llanos
Mar 15, 2011·Differentiation; Research in Biological Diversity·Ana KrtolicaSusan J Fisher
May 8, 2007·Journal of Reproductive Immunology·Debra S Goldman-Wohl, Simcha Yagel
May 27, 2003·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Patricia M Clissold, Roy Bicknell
Jun 14, 2005·Placenta·R K MillerB Huppertz
Sep 24, 2004·The International Journal of Biochemistry & Cell Biology·Paul Bischof, Irmgard Irminger-Finger
May 29, 2015·Journal of Cellular Biochemistry·Teresa OttoElke Winterhager
Oct 14, 2014·The American Journal of Pathology·Yan ZhouEmin Maltepe
Oct 2, 2007·American Journal of Obstetrics and Gynecology·Ramkrishna MehendaleRichard Leach
Apr 10, 2010·Systems Biology in Reproductive Medicine·Daniel A RappoleeYufen Xie
Jul 20, 2012·American Journal of Physiology. Endocrinology and Metabolism·M CocquebertT Fournier
Oct 20, 2005·Human Reproduction Update·J L JamesL W Chamley
Feb 20, 2014·Molecular Medicine Reports·Yan-Yan LuBao-Guo Xie
May 15, 2015·American Journal of Physiology. Endocrinology and Metabolism·Liliya M YamaleyevaK Bridget Brosnihan
May 11, 2004·American Journal of Physiology. Lung Cellular and Molecular Physiology·M C Tissot van PatotL Zwerdlinger
Oct 30, 2003·American Journal of Physiology. Renal Physiology·Sandra TurcotteRichard Beliveau
Jun 21, 2012·Molecular and Cellular Biochemistry·Jian-Ying XuHuan Jiang

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.