Skip to Main content Skip to Navigation
Theses

Etude de l'impact de la perte d'expression de PTEN sur la réponse au cetuximab et l'induction de l'angiogenèse par un modèle cellulaire de carcinome épidermoïde de la tête et du cou

Abstract : Cetuximab has been recently accepted as a single agent to treat recurrent and/or metastatic head and neck squamous cell carcinoma. However, modest efficacy of cetuximab used as a single agent has been reported on primary tumor. In many tumor types, loss of PTEN expression has been described to be associated to resistance to anti-EGFR therapies. Loss of PTEN expression is a frequent event in head and neck squamous cell carcinoma. This study is the first one to directly investigate the role of PTEN loss of expression in response of head and neck squamous cell carcinoma to cetuximab. PTEN-deficient cellular model shows that loss of PTEN expression leads to an overactivation of the signaling pathways ruling cell survival and proliferation but do not impact on cetuximab efficacy. According to our data, Cal 27 cells growth rather depends on PI3K/AKT activation than on EGFR. Observation of angiogenesis, using an aortic ring assay cultured in conditioned media, shows that endothelial sprouting is not dependent on VEGF. PTEN silencing in Cal 27 cells induces anti-angiogenic TSP1 and IGFBP 3 levels in the conditioned medium and reduces the sprouting induction ability by Cal 27 cells. Finally, it is likely that loss of PTEN expression is not a key event in head and neck squamous cell carcinoma tumorigenesis, but might be determinant when occurring as a late event. Taken together, our data suggest that loss of PTEN expression could be involved in initiating metastasis process in head and neck squamous cell carcinomas
Document type :
Theses
Complete list of metadatas

Cited literature [207 references]  Display  Hide  Download

https://hal.univ-lorraine.fr/tel-01746329
Contributor : Thèses Ul <>
Submitted on : Thursday, March 29, 2018 - 10:31:20 AM
Last modification on : Monday, April 16, 2018 - 10:41:51 AM
Long-term archiving on: : Thursday, September 13, 2018 - 12:08:25 PM

File

SCD_T_2010_0099_MRIOUAH.pdf
Files produced by the author(s)

Identifiers

  • HAL Id : tel-01746329, version 1

Collections

Citation

Jihane Mriouah. Etude de l'impact de la perte d'expression de PTEN sur la réponse au cetuximab et l'induction de l'angiogenèse par un modèle cellulaire de carcinome épidermoïde de la tête et du cou. Médecine humaine et pathologie. Université Henri Poincaré - Nancy 1, 2010. Français. ⟨NNT : 2010NAN10099⟩. ⟨tel-01746329⟩

Share

Metrics

Record views

30

Files downloads

849