Cargando…

Identification of the zinc finger 216 (ZNF216) in human carcinoma cells: a potential regulator of EGFR activity

Epidermal Growth Factor Receptor (EGFR), a member of the ErbB family of receptor tyrosine kinase (RTK) proteins, is aberrantly expressed or deregulated in tumors and plays pivotal roles in cancer onset and metastatic progression. ZNF216 gene has been identified as one of Immediate Early Genes (IEGs)...

Descripción completa

Detalles Bibliográficos
Autores principales: Mincione, Gabriella, Di Marcantonio, Maria Carmela, Tarantelli, Chiara, Savino, Luca, Ponti, Donatella, Marchisio, Marco, Lanuti, Paola, Sancilio, Silvia, Calogero, Antonella, Di Pietro, Roberta, Muraro, Raffaella
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5342714/
https://www.ncbi.nlm.nih.gov/pubmed/27732953
http://dx.doi.org/10.18632/oncotarget.12509
_version_ 1782513238131343360
author Mincione, Gabriella
Di Marcantonio, Maria Carmela
Tarantelli, Chiara
Savino, Luca
Ponti, Donatella
Marchisio, Marco
Lanuti, Paola
Sancilio, Silvia
Calogero, Antonella
Di Pietro, Roberta
Muraro, Raffaella
author_facet Mincione, Gabriella
Di Marcantonio, Maria Carmela
Tarantelli, Chiara
Savino, Luca
Ponti, Donatella
Marchisio, Marco
Lanuti, Paola
Sancilio, Silvia
Calogero, Antonella
Di Pietro, Roberta
Muraro, Raffaella
author_sort Mincione, Gabriella
collection PubMed
description Epidermal Growth Factor Receptor (EGFR), a member of the ErbB family of receptor tyrosine kinase (RTK) proteins, is aberrantly expressed or deregulated in tumors and plays pivotal roles in cancer onset and metastatic progression. ZNF216 gene has been identified as one of Immediate Early Genes (IEGs) induced by RTKs. Overexpression of ZNF216 protein sensitizes 293 cell line to TNF-α induced apoptosis. However, ZNF216 overexpression has been reported in medulloblastomas and metastatic nasopharyngeal carcinomas. Thus, the role of this protein is still not clearly understood. In this study, the inverse correlation between EGFR and ZNF216 expression was confirmed in various human cancer cell lines differently expressing EGFR. EGF treatment of NIH3T3 cells overexpressing both EGFR and ZNF216 (NIH3T3-EGFR/ZNF216), induced a long lasting activation of EGFR in the cytosolic fraction and an accumulation of phosphorylated EGFR (pEGFR) more in the nuclear than in the cytosolic fraction compared to NIH3T3-EGFR cells. Moreover, EGF was able to stimulate an increased expression of ZNF216 in the cytosolic compartment and its nuclear translocation in a time-dependent manner in NIH3T3-EGFR/ZNF216. A similar trend was observed in A431 cells endogenously expressing the EGFR and transfected with Znf216. The increased levels of pEGFR and ZNF216 in the nuclear fraction of NIH3T3-EGFR/ZNF216 cells were paralleled by increased levels of phospho-MAPK and phospho-Akt. Surprisingly, EGF treatment of NIH3T3-EGFR/ZNF216 cells induced a significant increase of apoptosis thus indicating that ZNF216 could sensitize cells to EGF-induced apoptosis and suggesting that it may be involved in the regulation and effects of EGFR signaling.
format Online
Article
Text
id pubmed-5342714
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher Impact Journals LLC
record_format MEDLINE/PubMed
spelling pubmed-53427142017-03-28 Identification of the zinc finger 216 (ZNF216) in human carcinoma cells: a potential regulator of EGFR activity Mincione, Gabriella Di Marcantonio, Maria Carmela Tarantelli, Chiara Savino, Luca Ponti, Donatella Marchisio, Marco Lanuti, Paola Sancilio, Silvia Calogero, Antonella Di Pietro, Roberta Muraro, Raffaella Oncotarget Research Paper Epidermal Growth Factor Receptor (EGFR), a member of the ErbB family of receptor tyrosine kinase (RTK) proteins, is aberrantly expressed or deregulated in tumors and plays pivotal roles in cancer onset and metastatic progression. ZNF216 gene has been identified as one of Immediate Early Genes (IEGs) induced by RTKs. Overexpression of ZNF216 protein sensitizes 293 cell line to TNF-α induced apoptosis. However, ZNF216 overexpression has been reported in medulloblastomas and metastatic nasopharyngeal carcinomas. Thus, the role of this protein is still not clearly understood. In this study, the inverse correlation between EGFR and ZNF216 expression was confirmed in various human cancer cell lines differently expressing EGFR. EGF treatment of NIH3T3 cells overexpressing both EGFR and ZNF216 (NIH3T3-EGFR/ZNF216), induced a long lasting activation of EGFR in the cytosolic fraction and an accumulation of phosphorylated EGFR (pEGFR) more in the nuclear than in the cytosolic fraction compared to NIH3T3-EGFR cells. Moreover, EGF was able to stimulate an increased expression of ZNF216 in the cytosolic compartment and its nuclear translocation in a time-dependent manner in NIH3T3-EGFR/ZNF216. A similar trend was observed in A431 cells endogenously expressing the EGFR and transfected with Znf216. The increased levels of pEGFR and ZNF216 in the nuclear fraction of NIH3T3-EGFR/ZNF216 cells were paralleled by increased levels of phospho-MAPK and phospho-Akt. Surprisingly, EGF treatment of NIH3T3-EGFR/ZNF216 cells induced a significant increase of apoptosis thus indicating that ZNF216 could sensitize cells to EGF-induced apoptosis and suggesting that it may be involved in the regulation and effects of EGFR signaling. Impact Journals LLC 2016-10-06 /pmc/articles/PMC5342714/ /pubmed/27732953 http://dx.doi.org/10.18632/oncotarget.12509 Text en Copyright: © 2016 Mincione et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Mincione, Gabriella
Di Marcantonio, Maria Carmela
Tarantelli, Chiara
Savino, Luca
Ponti, Donatella
Marchisio, Marco
Lanuti, Paola
Sancilio, Silvia
Calogero, Antonella
Di Pietro, Roberta
Muraro, Raffaella
Identification of the zinc finger 216 (ZNF216) in human carcinoma cells: a potential regulator of EGFR activity
title Identification of the zinc finger 216 (ZNF216) in human carcinoma cells: a potential regulator of EGFR activity
title_full Identification of the zinc finger 216 (ZNF216) in human carcinoma cells: a potential regulator of EGFR activity
title_fullStr Identification of the zinc finger 216 (ZNF216) in human carcinoma cells: a potential regulator of EGFR activity
title_full_unstemmed Identification of the zinc finger 216 (ZNF216) in human carcinoma cells: a potential regulator of EGFR activity
title_short Identification of the zinc finger 216 (ZNF216) in human carcinoma cells: a potential regulator of EGFR activity
title_sort identification of the zinc finger 216 (znf216) in human carcinoma cells: a potential regulator of egfr activity
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5342714/
https://www.ncbi.nlm.nih.gov/pubmed/27732953
http://dx.doi.org/10.18632/oncotarget.12509
work_keys_str_mv AT mincionegabriella identificationofthezincfinger216znf216inhumancarcinomacellsapotentialregulatorofegfractivity
AT dimarcantoniomariacarmela identificationofthezincfinger216znf216inhumancarcinomacellsapotentialregulatorofegfractivity
AT tarantellichiara identificationofthezincfinger216znf216inhumancarcinomacellsapotentialregulatorofegfractivity
AT savinoluca identificationofthezincfinger216znf216inhumancarcinomacellsapotentialregulatorofegfractivity
AT pontidonatella identificationofthezincfinger216znf216inhumancarcinomacellsapotentialregulatorofegfractivity
AT marchisiomarco identificationofthezincfinger216znf216inhumancarcinomacellsapotentialregulatorofegfractivity
AT lanutipaola identificationofthezincfinger216znf216inhumancarcinomacellsapotentialregulatorofegfractivity
AT sanciliosilvia identificationofthezincfinger216znf216inhumancarcinomacellsapotentialregulatorofegfractivity
AT calogeroantonella identificationofthezincfinger216znf216inhumancarcinomacellsapotentialregulatorofegfractivity
AT dipietroroberta identificationofthezincfinger216znf216inhumancarcinomacellsapotentialregulatorofegfractivity
AT muraroraffaella identificationofthezincfinger216znf216inhumancarcinomacellsapotentialregulatorofegfractivity