Blocking Epidermal Growth Factor Receptor Signaling in HTR-8/SVneo First Trimester Trophoblast Cells Results in Dephosphorylation of PKBα/AKT and Induces Apoptosis

We identified a major peptide signaling target of EGF/EGFR pathway and explored the consequences of blocking or activating this pathway in the first trimester extravillous trophoblast cells, HTR-8/SVneo. A global analysis of protein phosphorylation was undertaken using novel technology (Kinexus Kine...

Full description

Saved in:
Bibliographic Details
Main Authors: J. Bolnick, L. Albitar, L. L. Laidler, R. Abdullah, K. K. Leslie
Format: Article
Language:English
Published: Wiley 2011-01-01
Series:Obstetrics and Gynecology International
Online Access:http://dx.doi.org/10.1155/2011/896896
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1832545416527216640
author J. Bolnick
L. Albitar
L. L. Laidler
R. Abdullah
K. K. Leslie
author_facet J. Bolnick
L. Albitar
L. L. Laidler
R. Abdullah
K. K. Leslie
author_sort J. Bolnick
collection DOAJ
description We identified a major peptide signaling target of EGF/EGFR pathway and explored the consequences of blocking or activating this pathway in the first trimester extravillous trophoblast cells, HTR-8/SVneo. A global analysis of protein phosphorylation was undertaken using novel technology (Kinexus Kinetworks) that utilizes SDS-polyacrylamide minigel electrophoresis and multi-lane immunoblotting to permit specific and semiquantitative detection of multiple phosphoproteins. Forty-seven protein phosphorylation sites were queried, and the results reported based on relative phosphorylation at each site. EGF- and Iressa-(gefitinib, ZD1839, an inhibitor of EGFR) treated HTR-8/SVneo cells were subjected to immunoblotting and flow cytometry to confirm the phosphoprotein screen and to assess the effects of EGF versus Iressa on cell cycle and apoptosis. EGFR mediates the phosphorylation of important signaling proteins, including PKBα/AKT. This pathway is likely to be central to EGFR-mediated trophoblast survival. Furthermore, EGF treatment induces proliferation and inhibits apoptosis, while Iressa induces apoptosis.
format Article
id doaj-art-06eec46c31c842d3a49b597f298d99ec
institution Kabale University
issn 1687-9589
1687-9597
language English
publishDate 2011-01-01
publisher Wiley
record_format Article
series Obstetrics and Gynecology International
spelling doaj-art-06eec46c31c842d3a49b597f298d99ec2025-02-03T07:25:42ZengWileyObstetrics and Gynecology International1687-95891687-95972011-01-01201110.1155/2011/896896896896Blocking Epidermal Growth Factor Receptor Signaling in HTR-8/SVneo First Trimester Trophoblast Cells Results in Dephosphorylation of PKBα/AKT and Induces ApoptosisJ. Bolnick0L. Albitar1L. L. Laidler2R. Abdullah3K. K. Leslie4The Reproductive Molecular Biology Laboratory, Division of Maternal-Fetal Medicine, Departments of Obstetrics and Gynecology and Biochemistry and Molecular Biology, The University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USAThe Reproductive Molecular Biology Laboratory, Division of Maternal-Fetal Medicine, Departments of Obstetrics and Gynecology and Biochemistry and Molecular Biology, The University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USAThe Reproductive Molecular Biology Laboratory, Division of Maternal-Fetal Medicine, Departments of Obstetrics and Gynecology and Biochemistry and Molecular Biology, The University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USAThe Reproductive Molecular Biology Laboratory, Division of Maternal-Fetal Medicine, Departments of Obstetrics and Gynecology and Biochemistry and Molecular Biology, The University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USAThe Reproductive Molecular Biology Laboratory, Division of Maternal-Fetal Medicine, Departments of Obstetrics and Gynecology and Biochemistry and Molecular Biology, The University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USAWe identified a major peptide signaling target of EGF/EGFR pathway and explored the consequences of blocking or activating this pathway in the first trimester extravillous trophoblast cells, HTR-8/SVneo. A global analysis of protein phosphorylation was undertaken using novel technology (Kinexus Kinetworks) that utilizes SDS-polyacrylamide minigel electrophoresis and multi-lane immunoblotting to permit specific and semiquantitative detection of multiple phosphoproteins. Forty-seven protein phosphorylation sites were queried, and the results reported based on relative phosphorylation at each site. EGF- and Iressa-(gefitinib, ZD1839, an inhibitor of EGFR) treated HTR-8/SVneo cells were subjected to immunoblotting and flow cytometry to confirm the phosphoprotein screen and to assess the effects of EGF versus Iressa on cell cycle and apoptosis. EGFR mediates the phosphorylation of important signaling proteins, including PKBα/AKT. This pathway is likely to be central to EGFR-mediated trophoblast survival. Furthermore, EGF treatment induces proliferation and inhibits apoptosis, while Iressa induces apoptosis.http://dx.doi.org/10.1155/2011/896896
spellingShingle J. Bolnick
L. Albitar
L. L. Laidler
R. Abdullah
K. K. Leslie
Blocking Epidermal Growth Factor Receptor Signaling in HTR-8/SVneo First Trimester Trophoblast Cells Results in Dephosphorylation of PKBα/AKT and Induces Apoptosis
Obstetrics and Gynecology International
title Blocking Epidermal Growth Factor Receptor Signaling in HTR-8/SVneo First Trimester Trophoblast Cells Results in Dephosphorylation of PKBα/AKT and Induces Apoptosis
title_full Blocking Epidermal Growth Factor Receptor Signaling in HTR-8/SVneo First Trimester Trophoblast Cells Results in Dephosphorylation of PKBα/AKT and Induces Apoptosis
title_fullStr Blocking Epidermal Growth Factor Receptor Signaling in HTR-8/SVneo First Trimester Trophoblast Cells Results in Dephosphorylation of PKBα/AKT and Induces Apoptosis
title_full_unstemmed Blocking Epidermal Growth Factor Receptor Signaling in HTR-8/SVneo First Trimester Trophoblast Cells Results in Dephosphorylation of PKBα/AKT and Induces Apoptosis
title_short Blocking Epidermal Growth Factor Receptor Signaling in HTR-8/SVneo First Trimester Trophoblast Cells Results in Dephosphorylation of PKBα/AKT and Induces Apoptosis
title_sort blocking epidermal growth factor receptor signaling in htr 8 svneo first trimester trophoblast cells results in dephosphorylation of pkbα akt and induces apoptosis
url http://dx.doi.org/10.1155/2011/896896
work_keys_str_mv AT jbolnick blockingepidermalgrowthfactorreceptorsignalinginhtr8svneofirsttrimestertrophoblastcellsresultsindephosphorylationofpkbaaktandinducesapoptosis
AT lalbitar blockingepidermalgrowthfactorreceptorsignalinginhtr8svneofirsttrimestertrophoblastcellsresultsindephosphorylationofpkbaaktandinducesapoptosis
AT lllaidler blockingepidermalgrowthfactorreceptorsignalinginhtr8svneofirsttrimestertrophoblastcellsresultsindephosphorylationofpkbaaktandinducesapoptosis
AT rabdullah blockingepidermalgrowthfactorreceptorsignalinginhtr8svneofirsttrimestertrophoblastcellsresultsindephosphorylationofpkbaaktandinducesapoptosis
AT kkleslie blockingepidermalgrowthfactorreceptorsignalinginhtr8svneofirsttrimestertrophoblastcellsresultsindephosphorylationofpkbaaktandinducesapoptosis