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1.
J Cell Physiol ; 235(5): 4756-4765, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-31667838

RESUMEN

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.


Asunto(s)
Quimiocinas CXC/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Neoplasias del Cuello Uterino/enzimología , Adulto , Anciano , Animales , Apoptosis , Movimiento Celular , Proliferación Celular , Quimiocina CXCL5/genética , Quimiocina CXCL5/metabolismo , Quimiocinas CXC/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Células HeLa , Humanos , Ratones Desnudos , Persona de Mediana Edad , Invasividad Neoplásica , Comunicación Paracrina , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Transducción de Señal , Regulación hacia Arriba , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/patología , Proteína X Asociada a bcl-2/genética , Proteína X Asociada a bcl-2/metabolismo
3.
Sheng Li Xue Bao ; 64(4): 449-54, 2012 Aug 25.
Artículo en Inglés | MEDLINE | ID: mdl-22907306

RESUMEN

The present study was designed to investigate the role of protein kinase A (PKA) and phospholipase A(2) (PLA(2)) in the stimulating effect of adenosine on the basolateral 50 pS K(+) channels in the thick ascending limb (TAL) of the rat kidney. Under the anatomic microscope, the TAL was dissected. The current of 50 pS K(+) channels were recorded by patch clamp technology. The protein expression of phosphorylated PKA and phosphorylated PLA(2) were examined by Western blot. The results showed that cyclohexyladenosine (CHA), an analog of adenosine, increased the 50 pS K(+) channel activity (P < 0.05). In the presence of H8, an antagonist of PKA, CHA did not affect the 50 pS K(+) channel activity. In the presence of AACOCF3 (an antagonist of PLA(2)), CHA did not further increase the 50 pS K(+) channel activity. CHA increased phosphorylation level of PKA, whereas inhibited phosphorylation of PLA(2) in the TAL of the rat kidney (P < 0.01). Furthermore, after blocking the PLA(2) with AACOCF3, CHA still increased the expression of phosphorylated PKA. On the contrary, CHA did not obviously change the expression of phosphorylated PLA(2) after H8 pretreatment. The results suggest that the stimulation of basolateral 50 pS K(+) channels by CHA is mediated by the activation of PKA followed by the inhibition of PLA(2) in the TAL of the rat kidney.


Asunto(s)
Adenosina/farmacología , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Riñón/metabolismo , Fosfolipasas A2/metabolismo , Canales de Potasio/metabolismo , Adenosina/análogos & derivados , Animales , Ácidos Araquidónicos/farmacología , Riñón/efectos de los fármacos , Técnicas de Placa-Clamp , Ratas , Transducción de Señal
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