Amyloid Precursor Protein Overexpression in Down Syndrome Trophoblast Reduces Cell Invasiveness and Interferes with Syncytialization

The American Journal of Pathology
Oscar G W WongAnnie N Y Cheung

Abstract

The placentas of Down syndrome (DS) pregnancies exhibit morphologic and functional abnormalities. Although the increase in dosage of certain genes on chromosome 21 has been associated with the DS phenotype, the effects on placenta have seldom been studied. Herein, we examine the expression of four dosage-sensitive genes (APP, ETS2, SOD1, and HMGN1) in normal and DS placentas. We demonstrated significant overexpression of amyloid precursor protein (APP) in DS placentas at RNA and protein levels by real-time quantitative PCR, Western blot analysis, and immunohistochemistry. Inducible APP overexpression trophoblast cell line models were established using a Tet-On system. APP induction in HTR-8/SVneo dose-dependently decelerated cell growth, enhanced apoptosis, and reduced cell migration and invasion when compared with the uninduced controls. Concomitantly, decreased β-human chorionic gonadotropin in the culture medium was also detected on induction. Moreover, although forskolin treatment induced α/β-human chorionic gonadotropin and syncytin expression in BeWo cells, such induction of syncytialization was inhibited by APP overexpression. E-cadherin immunofluorescence also demonstrated a decrease in syncytia formation in forskolin-t...Continue Reading

References

Feb 1, 1990·Experimental Cell Research·B WiceA L Schwartz
Feb 7, 2004·The Journal of Clinical Endocrinology and Metabolism·J-L FrendoD Evain-Brion
Sep 25, 2004·American Journal of Medical Genetics. Part a·Alexi WrightSusan J Fisher
Oct 29, 2004·Nature Reviews. Genetics·Stylianos E AntonarakisSamuel Deutsch
Feb 10, 2007·Reproductive Biology and Endocrinology : RB&E·Laura LunghiFortunato Vesce
Dec 28, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Tracy L Young-PearseDennis J Selkoe
Sep 6, 2008·The American Journal of Pathology·Michelle K Y SiuAnnie N Y Cheung
Apr 21, 2009·Nature Methods·Jacek R WiśniewskiMatthias Mann
May 20, 2009·The Journal of Physiology·Christina M Scifres, D Michael Nelson
May 12, 2010·Acta Biochimica Et Biophysica Sinica·Xingxing FanHua Tang
May 27, 2010·PloS One·Juliet A MoncasterLee E Goldstein
Sep 1, 2011·Disease Models & Mechanisms·Eva Lana-ElolaVictor L J Tybulewicz
Dec 4, 2012·Autoimmunity Reviews·Marc E WekslerAntonia M W Coppus
Oct 23, 2015·American Journal of Reproductive Immunology : AJRI·Satish Kumar GuptaPiyush Chaudhary

❮ Previous
Next ❯

Citations

May 7, 2021·The Journal of Obstetrics and Gynaecology Research·Yanjie LuYuhong Li
Aug 8, 2021·Journal of Clinical Medicine·David G MorenoSylvia E Perez
Aug 17, 2021·Pediatric Neurology·Nina F Schor, Diana W Bianchi

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Cell Migration

Cell migration is involved in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. Here is the latest research.

Cadherins and Catenins

Cadherins (named for "calcium-dependent adhesion") are a type of cell adhesion molecule (CAM) that is important in the formation of adherens junctions to bind cells with each other. Catenins are a family of proteins found in complexes with cadherin cell adhesion molecules of animal cells: alpha-catenin can bind to β-catenin and can also bind actin. β-catenin binds the cytoplasmic domain of some cadherins. Discover the latest research on cadherins and catenins here.

Alzheimer's Disease: APP

Amyloid precursor protein (APP) proteolysis is critical for the development of Alzheimer's disease, a neurodegenerative disease associated with accumulation of amyloid plaques in the brain. Here is the latest research on APP and Alzheimer's disease.