Lack of oestrogenic inhibition of the nuclear factor-κB pathway in somatolactotroph tumour cells
| Autor: | Adriana Seilicovich, Mariela A. Moreno Ayala, Daniel Pisera, María Florencia Gottardo, Guadalupe Eijo, Marianela Candolfi, Sandra Zárate, Gabriela Jaita, María Laura Magri |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
medicine.medical_specialty
CIENCIAS MÉDICAS Y DE LA SALUD Lactotrophs Endocrinology Diabetes and Metabolism Mice Nude Apoptosis Nuclear factor κb Biology Mice Cellular and Molecular Neuroscience chemistry.chemical_compound Endocrinology stomatognathic system Cell Line Tumor Internal medicine PITUITARY medicine Animals Pituitary Neoplasms NF-kB Rats Wistar Tumor Necrosis Factor-alpha Endocrine and Autonomic Systems NF-kappa B Estrogens NF-κB Patología OESTROGENS Molecular biology Rats APOPTOSIS Medicina Básica chemistry Female Signal Transduction |
| DOI: | 10.1111/jne.12296/abstract |
| Popis: | Activation of nuclear factor (NF)-κB promotes cell proliferation and inhibits apoptosis. We have previously shown that oestrogens sensitise normal anterior pituitary cells to the apoptotic effect of tumour necrosis factor (TNF)-α by inhibiting NF-κB nuclear translocation. In the present study, we examined whether oestrogens also modulate the NF-κB signalling pathway and apoptosis in GH3 cells, a rat somatolactotroph tumour cell line. As determined by Western blotting, 17β-oestradiol (E2) (10−9 m) increased the nuclear concentration of NF-κB/p105, p65 and p50 in GH3 cells. However, E2 did not modify the expression of Bcl-xL, a NF-κB target gene. TNF-α induced apoptosis of GH3 cells incubated in either the presence or absence of E2. Inhibition of the NF-kB pathway using BAY 11-7082 (BAY) (5 μm) decreased the viability of GH3 cells and increased the percentage of terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL)-positive GH3 cells. BAY also increased TNF-α-induced apoptosis of GH3 cells, an effect that was further increased by an inhibitor of the c-Jun N-terminal protein kinase pathway, SP600125 (10 μm). We also analysed the role of the NF-κB signalling pathway on proliferation and apoptosis of GH3 tumours in vivo. The administration of BAY to nude mice bearing GH3 tumours increased the number of TUNEL-positive cells and decreased the number of proliferating GH3 cells. These findings suggest that GH3 cells lose their oestrogenic inhibitory action on the NF-κB pathway and that the pro-apoptotic effect of TNF-α on these tumour pituitary cells does not require sensitisation by oestrogens as occurs in normal pituitary cells. NF-κB was required for the survival of GH3 cells, suggesting that pharmacological inhibition of the NF-κB pathway could interfere with pituitary tumour progression. Fil: Eijo Alvarenga, Stella Guadalupe. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina; Argentina. Universidad de Buenos Aires; Argentina Fil: Gottardo, María Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina; Argentina. Universidad de Buenos Aires; Argentina Fil: Jaita, Gabriela Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina; Argentina. Universidad de Buenos Aires; Argentina Fil: Magri, María Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina; Argentina. Universidad de Buenos Aires; Argentina Fil: Moreno Ayala, Mariela Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina; Argentina. Universidad de Buenos Aires; Argentina Fil: Zarate, Sandra Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina; Argentina. Universidad de Buenos Aires; Argentina Fil: Candolfi, Marianela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina; Argentina. Universidad de Buenos Aires; Argentina Fil: Pisera, Daniel Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina; Argentina. Universidad de Buenos Aires; Argentina Fil: Seilicovich, Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina; Argentina. Universidad de Buenos Aires; Argentina |
| Databáze: | OpenAIRE |
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