TIAM1 Upregulation Confers NVP-BEZ235 Resistance to Breast Cancer Cells Through FGFR/STAT3 Pathway.
Biochem Genet
; 58(6): 953-965, 2020 Dec.
Article
em En
| MEDLINE
| ID: mdl-32671511
ABSTRACT
Breast cancer is the most common cancer in women worldwide, and advanced breast cancer is the leading cause of cancer death in women. In present study, we aim to investigate that role of T-cell lymphoma invasion and metastasis-inducing protein1 (TIAM1) on NVP-BEZ235 resistance to breast cancer MCF7 and MDA-MB-361 cells. Briefly, MCF7 and MDA-MB-361 cells were treated with NVP-BEZ235 and the relative expressions of TIAM1 at both mRNA level and protein level were determined by RT-PCR and western blot. In addition, MCF7 and MDA-MB-361 cells were transfected with TIAM1 knockdown or overexpression vector. Then the IC50 of NVP-BEZ235 on MCF7 and MDA-MB-361 cells were detected by MTT assay. Finally, FGFR/STAT3 pathway protein members were investigated by western blot. Consequently, we found that the mRNA and protein expressions of TIAM1 and FGFR1/3 were dramatically upregulated in NVP-BEZ235-treated group in both MCF7 and MDA-MB-361 cells. Interestingly, TIAM1 knockdown via shRNA decreased the IC50 of NVP-BEZ235 of breast cancer cells, while TIAM1 overexpression increased the IC50 of NVP-BEZ235 of breast cancer cells, which suggested that TIAM1 was one of the contributors for NVP-BEZ235 resistance. In addition, FGFR members including FGFR1/3 showed similar results to TIAM1. Importantly, FGFR inhibitor AZD4547 decreased the IC50 of NVP-BEZ235, which suggested that FGFR downregulation reduced the NVP-BEZ235 resistance to breast cancer cells. In summary, our present study revealed that TIAM1 conferred NVP-BEZ235 resistance to breast cancer cells via activating FGFR/STAT3 pathway.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Quinolinas
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Neoplasias da Mama
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Regulação Neoplásica da Expressão Gênica
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Regulação para Cima
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Resistencia a Medicamentos Antineoplásicos
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Receptor Tipo 1 de Fator de Crescimento de Fibroblastos
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Receptor Tipo 3 de Fator de Crescimento de Fibroblastos
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Fator de Transcrição STAT3
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Proteína 1 Indutora de Invasão e Metástase de Linfoma de Células T
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Imidazóis
Limite:
Female
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Humans
Idioma:
En
Revista:
Biochem Genet
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
China