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Master's Dissertation
DOI
https://doi.org/10.11606/D.85.2022.tde-10032023-124258
Document
Author
Full name
Soraia Barbosa de Oliveira
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2022
Supervisor
Committee
Marumo, Maria Helena Bellini (President)
Rocha, Fernanda Agostini
Sangioni, Luís Antônio
Title in Portuguese
Análise do perfil da expressão de canais de zinco no adenocarcinoma renal humano após quimioterapia
Keywords in Portuguese
CCRcc
perfil de expressão
transportadores
zinco
ZIP
ZnT
Abstract in Portuguese
O Carcinoma de células renais (CCR) representa, aproximadamente, 90% das neoplasias malignas renais, e é o mais agressivo dos tumores urológicos. Seu subtipo patológico mais frequente é o de células claras (CCRcc), frequentemente associado a mutação do gene supressor de tumor de Von Hippel-Liundal (VHL). O Temsirolimus (TEM) é um fármaco de terapia-alvo, com ação antiangiogênica e antiproliferativa que atua como um inibidor seletivo da via da Mammalian target of rapamycin (mTOR). O Zn é um elemento essencial para o metabolismo e homeostase celular. A família de transportadores responsáveis pelo controle homeostático do Zn são o ZnT e a família de transportadores ZIP. Dada a a importância do elemento Zn para a homeostase celular e a escassez de trabalhos encontrados sobre os mecanismos de controle de sua homeostase, o objetivo deste trabalho foi avaliar o perfil da expressão dos transportadores de Zn em células normais do túbulo proximal renal e no adenocarcinoma renal humano de células claras e o perfil da expressão dos transportadores das células do adenocarcinoma renal após o tratamento com TEM. Desta forma, foi verificada a avaliação da expressão do RNAm dos canais de Zn das amostras HK-2, 786-0 e 786-0/TEM pela técnica de Real Time q-PCR e a avaliação da expressão proteica dos grupos de amostra pela técnica de Western Blotting. Houve concordância entre resultados das duas técnicas empregadas. Verificou-se uma diminuição significativa na expressão dos canais ZnT1 e ZIP10 e um aumento significativo na expressão do canal ZIP11 na linhagem 786-0 quando comparado ao HK-2. Após o tratamento da linhagem 786-0, os canais ZnT4, ZIP10, ZIP11 e ZIP14 apresentaram uma diminuição significativa. O único canal que não apresentou diferença de expressão entre os grupos avaliados foi o ZIP4. Os resultados obtidos apresentam uma diferença no perfil de expressão entre a linhagem tumoral e a linhagem normal. Observou-se que o tratamento quimioterápico modulou a expressão dos canais transportadores de forma negativa.
Title in English
Analysis of zinc channels expression profile in human renal adenocarcinoma after chemotherapy
Keywords in English
CCRcc
expression profile
transporters
zinc
ZIP
ZnT
Abstract in English
Renal cell carcinoma (RCC) accounts for approximately 90% of malignant renal neoplasms, and is the most aggressive urological tumor. Its most frequent pathological subtype is clear cell (ccRCC), often associated with Von Hippel-Loundal (VHL) tumor suppressor gene mutation. Temsirolimus (TEM) is a targeted therapy drug with antiangiogenic and antiproliferative action that acts as a selective inhibitor of the Mammalian target of rapamycin (mTOR) pathway. Zn is an essential element for cellular metabolism and homeostasis. The family of transporters responsible for the homeostatic control of Zn are ZnT and the ZIP family of transporters. Given the importance of the element Zn for cellular homeostasis and the scarcity of works found on the control mechanisms of its homeostasis, the objective of this work was to evaluate the expression profile of Zn transporters in normal cells of the proximal renal tubule and in renal adenocarcinoma human clear cell tumor and transporter expression profile of renal adenocarcinoma cells after treatment with TEM. In this way, the evaluation of the expression of the mRNA of the Zn channels of the samples HK-2, 786-0 and 786-0/TEM was verified by the technique of Real Time q-PCR and the evaluation of the protein expression of the sample groups by the technique by Western Blotting. There was agreement between the results of the two techniques employed. There was a significant decrease in the expression of the ZnT1 and ZIP10 channels and a significant increase in the expression of the ZIP11 channel in the 786-0 strain when compared to HK-2. After the treatment of the 786-0 strain, the ZnT4, ZIP10, ZIP11 and ZIP14 channels showed a significant decrease. The only channel that did not show difference in expression between the evaluated groups was ZIP4. The results obtained show a difference in the expression profile between the tumor cell line and the normal cell line. It was observed that the chemotherapy treatment modulated the expression of the transporter channels in a negative way.
 
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Publishing Date
2023-03-16
 
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