Paracrine Stimulation of P2X7 Receptor by ATP Activates a Proliferative Pathway in Ovarian Carcinoma Cells
Por:
Vázquez-Cuevas F.G., Martínez-Ramírez A.S., Robles-Martínez L., Garay E., García-Carrancá A., Pérez-Montiel D., Castaneda-Garcia, C, Arellano R.O.
Publicada:
1 nov 2014
Resumen:
P2X7 is a purinergic receptor-channel; its activation by ATP elicits a
broad set of cellular actions, from apoptosis to signals for survival.
Here, P2X7 expression and function was studied in human ovarian
carcinoma (OCA) cells, and biopsies from non-cancerous and cancer
patients were analyzed by immunohistochemistry. Ovarian surface
epithelium in healthy tissue expressed P2X7 at a high level that was
maintained throughout the cancer. The cell lines SKOV-3 and CAOV-3 were
used to investigate P2X7 functions in OCA. In SKOV-3 cells, selective
stimulation of P2X7 by 2(3)-O-(4-benzoylbenzoyl)
adenosine-5-triphosphate (BzATP) induced a dose-dependent increase of
intracellular Ca2+ concentration ([Ca2+](i)) but not cell death.
Instead, BzATP increased the levels of phosphorylated ERK and AKT (pERK
and pAKT), with an EC50 of 44 +/- 2 and 1.27 +/- 0.5M, respectively; 10M
BzATP evoked a maximum effect within 15min that lasted for 120min.
Interestingly, basal levels of pERK and pAKT were decreased in the
presence of apyrase in the medium, strongly suggesting an endogenous,
ATP-mediated phenomenon. Accordingly: (i) mechanically stimulated cells
generated a [Ca2+](i) increase that was abolished by apyrase; (ii)
apyrase induced a decrease in culture viability, as measured by the MTS
assay for mitochondrial activity; and (iii) incubation with 10M
AZ10606120, a specific P2X7 antagonist and transfection with the
dominant negative P2X7 mutant E496A, both reduced cell viability to 70.1
+/- 8.9% and to 76.5 +/- 5%, respectively, of control cultures. These
observations suggested that P2X7 activity was auto-induced through ATP
efflux; this increased pERK and pAKT levels that generated a positive
feedback on cell viability. J. Cell. Biochem. 115: 1955-1966, 2014. (c)
2014 Wiley Periodicals, Inc.
Filiaciones:
Vázquez-Cuevas F.G.:
Univ Nacl Autonoma Mexico, Inst Neurobiol, Dept Neurobiol Celular & Mol, Juriquilla Queretaro 76230, Mexico
Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Universidad Nacional Autõnoma de México, Boulevard Juriquilla 3001, Juriquilla Querétaro, CP 76230, Mexico
Martínez-Ramírez A.S.:
Univ Nacl Autonoma Mexico, Inst Neurobiol, Dept Neurobiol Celular & Mol, Juriquilla Queretaro 76230, Mexico
Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Universidad Nacional Autõnoma de México, Boulevard Juriquilla 3001, Juriquilla Querétaro, CP 76230, Mexico
Robles-Martínez L.:
Univ Nacl Autonoma Mexico, Inst Neurobiol, Dept Neurobiol Celular & Mol, Juriquilla Queretaro 76230, Mexico
Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Universidad Nacional Autõnoma de México, Boulevard Juriquilla 3001, Juriquilla Querétaro, CP 76230, Mexico
Garay E.:
Univ Nacl Autonoma Mexico, Inst Neurobiol, Dept Neurobiol Celular & Mol, Juriquilla Queretaro 76230, Mexico
Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Universidad Nacional Autõnoma de México, Boulevard Juriquilla 3001, Juriquilla Querétaro, CP 76230, Mexico
García-Carrancá A.:
Univ Nacl Autonoma Mexico, Inst Invest Biomed, Unidad Invest Biomed Canc, Lab Virus & Canc, Tlalpan 14080, DF, Mexico
Laboratorio de Virus y Cáncer, Unidad de Investigaciõn Biomédica en Cáncer, Instituto de Investigaciones Biomédicas, Universidad Nacional Autõnoma de México, Av. San Fernando #22, Colonia Secciõn XVI, Tlalpan, CP 14080, DF, Mexico
Divisiõn de Investigaciõn Básica, Instituto Nacional de Cancerología, Secretaría de Salud, Av. San Fernando #22, Colonia Secciõn XVI, México Tlalpan, CP 14080, DF, Mexico
Pérez-Montiel D.:
Departamento de Patología, Instituto Nacional de Cancerología, Secretaría de Salud, México Av. San Fernando #22, Colonia Secciõn XVI, Tlalpan, CP 14080, DF, Mexico
Castaneda-Garcia, C:
Univ Nacl Autonoma Mexico, Inst Neurobiol, Dept Neurobiol Celular & Mol, Juriquilla Queretaro 76230, Mexico
Arellano R.O.:
Univ Nacl Autonoma Mexico, Inst Neurobiol, Dept Neurobiol Celular & Mol, Juriquilla Queretaro 76230, Mexico
Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Universidad Nacional Autõnoma de México, Boulevard Juriquilla 3001, Juriquilla Querétaro, CP 76230, Mexico
|