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Doctoral Thesis
DOI
10.11606/T.87.2009.tde-30042010-093125
Document
Author
Full name
Simone Aparecida de Bessa Garcia
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2009
Supervisor
Committee
Nagai, Maria Aparecida (President)
Folgueira, Maria Aparecida Azevedo Koike
Maria, Durvanei Augusto
Moreira Filho, Carlos Alberto
Pueyo, Shigueko Sonohara Troyano
Title in Portuguese
Estudo da interação entre vias de sinalização dos estrógenos e fatores de crescimento  no controle da transcrição dos genes HNRPK, PAWR e PHLDA1
Keywords in Portuguese
Estradiol
Expressão gênica
Fatores de crescimento
Neoplasias mamárias
Vias de sinalização intracelulares
Abstract in Portuguese
A interação entre as vias de sinalização dos estrógenos e fatores de crescimento está relacionada a maior agressividade dos tumores de mama. Assim, o objetivo deste trabalho foi verificar a interação entre as vias do E2 e do EGF no controle da expressão dos genes HNRPK, PAWR e PHLDA1 nas células MCF-7 (ER+) e MDA-MB-231 (ER-). Nas células MCF-7, o EGF e o E2 diminuíram a expressão do PAWR e aumentaram a expressão de PHLDA1. A inibição do ER pelo ICI resultou no aumento da expressão de PAWR sendo que a adição do E2 ou do EGF diminuiu sua expressão sem retomar os níveis observados nos tratamentos com E2 ou EGF isoladamente. Para o gene PHLDA1, o efeito do E2 e do EGF não variou após o tratamento com ICI. Nas células MDA-MB-231, a ação do EGF foi mais efetiva sobre a expressão de PAWR. A via ERK1/2 é importante na ativação do ER pelo EGF. O efeito do EGF sobre o PHLDA1 ocorre através da ativação das vias ERK1/2 e p38 MAPK. Estes resultados mostram a interação entre as vias do E2 e do EGF no controle da expressão do PAWR, mas não do PHLDA1.
Title in English
Study to evaluate the crosstalk between estrogens and growth factors pathways on the transcriptional regulation of HNRPK, PAWR and PHLDA1.
Keywords in English
Estradiol
Gene expression
Growth factors
Intracellular pathways
Mammary neoplasms
Abstract in English
The crosstalk between estrogens and growth factors pathways has been associated with breast cancer aggressiveness. Based on this, the present study aimed to determine the possible crosstalk between E2 and EGF pathways on the HNRPK, PAWR and PHLDA1 expression regulation in MCF-7 (ER+) and MDA-MB-231 (ER-) cells. In MCF-7 cells, treatments with E2 and EGF decreased PAWR expression and increased PHLDA1 expression. The ER inhibition by the ICI treatment resulted in increased PAWR expression. The E2 or EGF addition down-regulated its expression without a return to the levels observed after the E2 or EGF treatments alone. To the PHLDA1 gene, the effect of E2 and EGF treatments did not change after the ICI treatment. In MDA-MB-231 cells, the EGF effect was more significant on the PAWR gene expression control. The ERK1/2 pathway is important to the ER activation by EGF. The EGF effect over the PHLDA1 is dependent on the ERK1/2 and p38 MAPK activation. These findings suggest a crosstalk between E2 and EGF pathways on the PAWR expression control but not to PHLDA1.
 
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Publishing Date
2010-05-26
 
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