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Doctoral Thesis
DOI
10.11606/T.87.2013.tde-06112013-104247
Document
Author
Full name
Juliana Laino do Val Carneiro
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2013
Supervisor
Committee
Dias Neto, Emmanuel (President)
Carraro, Dirce Maria
Nagai, Maria Aparecida
Sogayar, Mari Cleide
Strauss, Bryan Eric
Title in Portuguese
Avaliação do papel dos miRNAs -221, -222 e -4728-3p em células-tronco tumorais derivadas de linhagens celulares de cancer de mama HER2+.
Keywords in Portuguese
Camundongos
Células cultivadas de tumor
Células-tronco
Neoplasias mamárias
Abstract in Portuguese
CSCs, caracterizadas pela alta atividade da ALDH1 e expressão (ou não) de marcadores de células-tronco embrionárias OCT-4, NANOG, SOX2, KLF4, LIN2, estão presentes em tumores de mama HER2+. Mamosferas são estruturas celulares esferóides in vitro enriquecidas em CSCs. Neste trabalho, buscou-se um melhor entendimento do papel dos miRNAs -221, -222 e -4728-3p na biologia das CSCs. Foi observado alto percentual de células ALDH1+ (citometria) em mamosferas das linhagens MCF-7, SKBR3 e BT-474; alta expressão (qRT-PCR) de miR-221 e -222 em mamosferas da linhagem MCF-7 e de tumores de pacientes, além de alta expressão de HER2 em mamosferas das linhagens MCF-7 e SKBR3. A MFE de células MCF-7 mostrou-se aumentada após a indução (com lentivetores) da superexpressão dos miRNAs -221 e -222. A resistência ao quimioterápico paclitaxel estava aumentada em mamosferas que superexpressavam o miRNA-222. A superexpressão de miR-4728-3p, localizado em um intron de HER2, levou a um aumento das subpopulações ALDH1+ em duas linhagens celulares reforçando seu envolvimento com a biologia de CSCs.
Title in English
Evaluation of the role of miRNAs -221, -222 e -4728-3p in breast cancer stem cells derived from HER2+ cell lines.
Keywords in English
Breast neoplasms
Cultured tumor cells
Mice
Stem cells
Abstract in English
CSCs, characterized by high activity of ALDH1 and high (or not) expression of embryonic stem cell markers OCT-4, NANOG, SOX2, KLF4, LIN28 are present in tumors with HER2 amplification. Mammospheres are spheroid cell structures in vitro enriched by CSCs. In this study, we aim to contribute to the better understanding the role of miRNAs -221, 222, 4728-3p in the the biology of CSCs. We observed high percentage of ALDH+ cells (cytometry) in mammospheres of MCF-7, SKBR3 and BT-474 cell lines; high expression (qRT-PCR) of miR-221 and -222 in mammospheres of MCF-7 cell line and cells derived from patients, moreover HER2 is upregulated in mammospheres from MCF-7 and SKBR3 cell lines. MFE is higher in MCF-7 cell line after induction (with lentivectors) of miR-221 and -222 expression. The resistance to paclitaxel was increased in mammopheres that were overexpressing miRNA-222. Overexpression of miR-4728-3p, located in an intron of HER2 gene, induced the increment of ALDH1+ subpopulations in two cell lines, reinforcing its role in the biology of CSCs.
 
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Release Date
2018-01-16
Publishing Date
2014-01-16
 
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