Document Detail


Cellular response to cetuximab in PTEN-silenced head and neck squamous cell carcinoma cell line.
MedLine Citation:
PMID:  21042725     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The implication of loss of PTEN expression in resistance to targeted therapy has already been described in many tumor types. The absence of response to anti-EGFR agents in PTEN-deficient tumors relies on persistent activation of signaling pathways downstream of pEGFR. To investigate the role of PTEN loss of expression in head and neck squamous cell carcinoma (HNSCC) response to cetuximab, we used siRNA in Cal 27 cells and then evaluated key signaling protein activation (pAKT and pERK 1/2) as well as cell viability and proliferation. PTEN silencing in Cal 27 cells led to a constitutive activation of signaling pathways evidenced by a strong increase in pAKT and pERK 1/2 expression. Moreover, PTEN-silenced cells did not show any significant changes either in cell viability or proliferation, only slight modifications on cell cycle. Additionally and unpredictably, our results indicated that PTEN silencing, led to a drastic reduction in pEGFR expression whereas total EGFR level did not significantly vary. Strikingly, despite this overactivation of signaling pathways ruling cell survival and proliferation in siPTEN cells, cetuximab fully exerted pAKT and pERK 1/2 inhibition of expression, similarly to its effect in untransfected Cal 27 cells. In conclusion, our study established that in Cal 27 cells, cetuximab keeps full ability to inhibit EGFR-dependent mechanisms, as shown by a decreased pAKT and pERK 1/2 level of expression, despite a strong PTEN silencing-induced overactivation. In Cal 27 cells, loss of PTEN expression does not lead to a loss of cetuximab efficacy in inhibiting EGFR-downstream signaling pathways, contrarily to data shown in previous works conducted in other tumor types.
Authors:
Jihane Mriouah; Cedric Boura; Sophie Pinel; Anne-Sophie Chretien; Alexandre Fifre; Jean-Louis Merlin; Beatrice Faivre
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Publication Detail:
Type:  Evaluation Studies; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of oncology     Volume:  37     ISSN:  1791-2423     ISO Abbreviation:  Int. J. Oncol.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-11-02     Completed Date:  2011-02-24     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  9306042     Medline TA:  Int J Oncol     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  1555-63     Citation Subset:  IM    
Affiliation:
EA 4421 SiGReTO Signalisation, Genomique et Recherche Translationnelle en Oncologie, UHP-Nancy 1, Nancy-Universite, 54505 Vandoeuvre-les-Nancy, France.
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MeSH Terms
Descriptor/Qualifier:
Antibodies, Monoclonal / pharmacology,  therapeutic use*
Antinematodal Agents / pharmacology,  therapeutic use
Carcinoma / genetics,  metabolism,  pathology,  therapy
Carcinoma, Squamous Cell
Cell Line, Tumor
Cell Proliferation / drug effects
Cell Survival / drug effects,  genetics
Combined Modality Therapy
Drug Resistance, Neoplasm / drug effects,  genetics
Genetic Therapy / methods
Head and Neck Neoplasms / genetics,  metabolism,  pathology,  therapy
Humans
Immunotherapy / methods
Neoplasms, Squamous Cell / genetics,  metabolism,  pathology,  therapy
PTEN Phosphohydrolase / antagonists & inhibitors,  genetics*
RNA Interference* / physiology
RNA, Small Interfering / genetics,  pharmacology
Treatment Outcome
Tumor Markers, Biological / analysis,  metabolism
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Antinematodal Agents; 0/RNA, Small Interfering; 0/Tumor Markers, Biological; EC 3.1.3.48/PTEN protein, human; EC 3.1.3.67/PTEN Phosphohydrolase; PQX0D8J21J/cetuximab

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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