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Doctoral Thesis
DOI
https://doi.org/10.11606/T.42.2016.tde-25022016-095442
Document
Author
Full name
Camila Lauand
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2015
Supervisor
Committee
Santelli, Glaucia Maria Machado (President)
Colquhoun, Alison
Gama, Patricia
Ionta, Marisa
Maria, Durvanei Augusto
Title in Portuguese
Avaliação da proliferação e migração celular mediadas pela ativação do EGFR em linhagens celulares de câncer de pulmão cultivadas como monocamadas e esferoides.
Keywords in Portuguese
Câncer de pulmão
Esferoides
Fator de crescimento epidérmico
Inibidor de tirosina quinase
Migração celular
Receptor do fator de crescimento epidérmico
Abstract in Portuguese
O presente estudo comparou os efeitos da ativação e inibição do EGFR em duas linhagens de câncer de pulmão, cultivadas em monocamada ou esferoides. Os esferoides foram cultivados sem elementos de matriz extracelular. As células A549 e HK2 apresentaram, respectivamente, 3 e 6 cópias do gene ErbB1 por núcleo, embora a expressão de EGFR seja menor nas células HK2. A ativação de EGFR por EGF ou inibição por AG1478 não promoveu mudanças na proliferação celular. Entretanto, as células cultivadas em monocamada, estimuladas com EGF, exibiram alterações na disposição dos microfilamentos de actina e aumento na velocidade de migração celular. UO126 e LY294002 foram adicionados às culturas para inibir, respectivamente, as vias ERK e Akt. A linhagem A549, cultivada em monocamada, não apresentou envolvimento das vias de sinalização de ERK e Akt na migração celular induzida por EGF, mas foi observado o envolvimento dessas vias nos esferoides. Já a linhagem HK2 apresentou o envolvimento de Akt para promover a migração celular após estímulo com EGF nas duas formas de cultivo.
Title in English
Evaluation of cell proliferation and migration mediated by EGFR activation in lung cancer cell lines grown as monolayers and spheroids.
Keywords in English
Cell migration
Epidermal growth factor receptor
Epidermal growth fator
Lung câncer
Spheroid
Tyrosine kinase inhibitor
Abstract in English
This study compared the effects of activation and inhibition of EGFR in two cell lines of lung cancer, grown in monolayer or spheroids. Spheroids were cultured without extracellular matrix components. HK2 and A549 cells showed, respectively, 3 and 6 ErbB1 gene copies per nucleus, while EGFR expression is lower in the HK2 cells. The activation by EGF or EGFR inhibition by AG1478 did not cause changes in cell proliferation. However, cells cultured in monolayers stimulated with EGF, showed changes in the arrangement of actin microfilaments and increased the speed of cell migration. UO126 and LY294002 were added to the cultures to inhibit, respectively, the ERK and Akt pathways. A549 cells grown in monolayer did not show involvement of ERK and Akt signaling pathways in the cell migration induced by EGF, but was observed involvement of such pathways in the spheroids. HK2 cells showed involvement of Akt to promote cell migration after EGF stimulation in monolayers and in spheroids.
 
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Publishing Date
2016-03-14
 
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