title: Identification of the zinc finger 216 (ZNF216) in human carcinoma cells: a potential regulator of EGFR activity.
abstract: 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.
authors.affiliation: Department of Medical, Oral and Biotechnological Sciences, University "G. d'Annunzio" Chieti-Pescara, Italy.|Center for Aging Science and Translational Medicine (CeSI-MeT), Chieti, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Mincione
authors.affiliation: Department of Medical, Oral and Biotechnological Sciences, University "G. d'Annunzio" Chieti-Pescara, Italy.
authors.forename: Maria Carmela
authors.initials: MC
authors.lastname: Di Marcantonio
authors.affiliation: Department of Medical, Oral and Biotechnological Sciences, University "G. d'Annunzio" Chieti-Pescara, Italy.|Current Address: Lymphoma and Genomics Research Program, IOR Institute of Oncology Research, Bellinzona, Switzerland.
authors.forename: Chiara
authors.initials: C
authors.lastname: Tarantelli
authors.affiliation: Department of Medical, Oral and Biotechnological Sciences, University "G. d'Annunzio" Chieti-Pescara, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Savino
authors.affiliation: Department of Medico-Surgical Sciences and Biotechnologies, University of Rome Sapienza, Latina, Italy.
authors.forename: Donatella
authors.initials: D
authors.lastname: Ponti
authors.affiliation: Center for Aging Science and Translational Medicine (CeSI-MeT), Chieti, Italy.|Department of Medicine and Ageing Sciences, University "G. d'Annunzio", Chieti-Pescara, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Marchisio
authors.affiliation: Center for Aging Science and Translational Medicine (CeSI-MeT), Chieti, Italy.|Department of Medicine and Ageing Sciences, University "G. d'Annunzio", Chieti-Pescara, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Lanuti
authors.affiliation: Department of Pharmacy, University "G. d'Annunzio", Chieti-Pescara, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Sancilio
authors.affiliation: Department of Medico-Surgical Sciences and Biotechnologies, University of Rome Sapienza, Latina, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Calogero
authors.affiliation: Department of Medicine and Ageing Sciences, University "G. d'Annunzio", Chieti-Pescara, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Di Pietro
authors.affiliation: Department of Medical, Oral and Biotechnological Sciences, University "G. d'Annunzio" Chieti-Pescara, Italy.|Center for Aging Science and Translational Medicine (CeSI-MeT), Chieti, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Muraro
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D000066630:Ectopic Gene Expression; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D010766:Phosphorylation / Q000187:drug effects; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011485:Protein Binding; D021381:Protein Transport; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D059748:Proteolysis; D015398:Signal Transduction
chemical_list: D011506:Proteins; C114488:ZFAND5 protein, human; D004815:Epidermal Growth Factor; D011065:Poly(ADP-ribose) Polymerases; D066246:ErbB Receptors
keywords: EGFR; ZNF216; nuclear EGFR