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J Cell Physiol ; 235(5): 4756-4765, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31667838

RESUMO

CXCL3 belongs to the CXC-type chemokine family and is known to play a multifaceted role in various human malignancies. While its clinical significance and mechanisms of action in uterine cervical cancer (UCC) remain unclear. This investigation demonstrated that the UCC cell line HeLa expressed CXCL3, and strong expression of CXCL3 was detected in UCC tissues relative to nontumor tissues. In addition, CXCL3 expression was strongly correlated with CXCL5 expression in UCC tissues. In vitro, HeLa cells overexpressing CXCL3, HeLa cells treated with exogenous CXCL3 or treated with conditioned medium from WPMY cells overexpressing CXCL3, exhibited enhanced proliferation and migration activities. In agreement with these findings, CXCL3 overexpression was also associated with the generation of HeLa cell tumor xenografts in athymic nude mice. Subsequent mechanistic studies demonstrated that CXCL3 overexpressing influenced the expression of extracellular signal-regulated kinase (ERK) signaling pathway associated genes, including ERK1/2, Bcl-2, and Bax, whereas the CXCL3-induced proliferation and migration effects were attenuated by exogenous administration of the ERK1/2 blocker PD98059. The data of the current investigation support that CXCL3 appears to hold promise as a potential tumor marker and interference target for UCC.


Assuntos
Quimiocinas CXC/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Neoplasias do Colo do Útero/enzimologia , Adulto , Idoso , Animais , Apoptose , Movimento Celular , Proliferação de Células , Quimiocina CXCL5/genética , Quimiocina CXCL5/metabolismo , Quimiocinas CXC/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Células HeLa , Humanos , Camundongos Nus , Pessoa de Meia-Idade , Invasividade Neoplásica , Comunicação Parácrina , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Transdução de Sinais , Regulação para Cima , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
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