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Master's Dissertation
DOI
https://doi.org/10.11606/D.42.2015.tde-05102015-190307
Document
Author
Full name
Maíra de Assis Lima
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2015
Supervisor
Committee
Freitas, Vanessa Morais (President)
Borella, Maria Ines
Cardoso, Alexandre Bruni
Title in Portuguese
Influência dos hormônios esteroidais na migração, invasão e expressão das proteases ADAMTS 1 e 4 em células derivadas de tumores de ovários.
Keywords in Portuguese
ADAMTS 1 e 4
Câncer de ovário
Hormônios
Matriz extracelular
Metaloproteinases da matriz
Abstract in Portuguese
O câncer de ovário é uma neoplasia ginecológica e alternâncias hormonais poderiam ter um papel na manifestação da doença. As ADAMTS´s são proteases secretadas dependentes de Zn2+/Ca2+. Nosso objetivo foi avaliar se há Influência de hormônios sexuais nos níveis de expressão de mRNA, proteínas e distribuição de ADAMTS 1 e 4 e alteração na migração e invasão em células tumorais humanas de ovário. As linhagens foram tratadas com progesterona, estrógeno ou testosterona e o controle não recebeu tratamento. O estrógeno e a testosterona induziram uma menor e a progesterona uma maior expressão gênica de ADAMTS 1 e 4 em relação ao controle para a linhagem ES-2. A progesterona foi capaz de induzir aumento nos níveis proteicos de ADAMTS 1 e 4 no lisado de ambas as linhagens. A progesterona diminuiu a capacidade migratória e de invasão das linhagens. Observamos na imunofluorescência ADAMTS 1 no núcleo das células. Concluímos que a progesterona regula a expressão das ADAMTS 1 e 4, e reduz a invasão e migração de células derivadas de câncer de ovário.
Title in English
Influence of steroid hormones in the migration, invasion and expression of ADAMTS 1 and 4 proteases in ovary cancer cells.
Keywords in English
ADAMTS 1 and 4
Extracellular matrix
Hormones
Matrix metalloproteinases
Ovarian cancer
Abstract in English
Ovarian carcinoma is the leading cause of gynecological neoplastic death, being associated primarily with deregulation of sex hormones. ADAMTS are secreted proteases. Our aim is to assess whether sex hormones would affect ADAMTS1 and 4 expressions in ovarian cancer cells. Estrogen and testosterone induced a decrease on gene expression of ADAMTS 1 and 4 compared to the control for the ES-2 cell line, while progesterone led to an increase in the mRNA levels of these same proteases. Progesterone increases ADAMTS's protein levels in the lysate and in conditioned medium from NIH-OVCAR-3 and in the lysate from ES-2 cells. Immunofluorescence showed ADAMTS 1 located at the cell nucleus. NIH-OVCAR-3 cells treated with progesterone exhibited decrease migratory activity compared to control and ES-2 exhibited decrease invasion activity. We conclude that progesterone modulates ADAMTS1 and 4 levels in ovarian cancer cell lines and decrease migratory and invasion behavior in ovarian cancer cells.
 
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Publishing Date
2015-10-08
 
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