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Lack of Oestrogenic Inhibition of the Nuclear Factor-κB Pathway in Somatolactotroph Tumour Cells.
J Neuroendocrinol. 2015 Sep; 27(9):692-701.JN

Abstract

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.

Authors+Show Affiliations

Instituto de Investigaciones Biomédicas, Universidad de Buenos Aires-CONICET, Buenos Aires, Argentina.Instituto de Investigaciones Biomédicas, Universidad de Buenos Aires-CONICET, Buenos Aires, Argentina.Instituto de Investigaciones Biomédicas, Universidad de Buenos Aires-CONICET, Buenos Aires, Argentina.Instituto de Investigaciones Biomédicas, Universidad de Buenos Aires-CONICET, Buenos Aires, Argentina.Instituto de Investigaciones Biomédicas, Universidad de Buenos Aires-CONICET, Buenos Aires, Argentina.Instituto de Investigaciones Biomédicas, Universidad de Buenos Aires-CONICET, Buenos Aires, Argentina.Instituto de Investigaciones Biomédicas, Universidad de Buenos Aires-CONICET, Buenos Aires, Argentina.Instituto de Investigaciones Biomédicas, Universidad de Buenos Aires-CONICET, Buenos Aires, Argentina.Instituto de Investigaciones Biomédicas, Universidad de Buenos Aires-CONICET, Buenos Aires, Argentina.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26052658

Citation

Eijo, G, et al. "Lack of Oestrogenic Inhibition of the Nuclear Factor-κB Pathway in Somatolactotroph Tumour Cells." Journal of Neuroendocrinology, vol. 27, no. 9, 2015, pp. 692-701.
Eijo G, Gottardo MF, Jaita G, et al. Lack of Oestrogenic Inhibition of the Nuclear Factor-κB Pathway in Somatolactotroph Tumour Cells. J Neuroendocrinol. 2015;27(9):692-701.
Eijo, G., Gottardo, M. F., Jaita, G., Magri, M. L., Moreno Ayala, M., Zárate, S., Candolfi, M., Pisera, D., & Seilicovich, A. (2015). Lack of Oestrogenic Inhibition of the Nuclear Factor-κB Pathway in Somatolactotroph Tumour Cells. Journal of Neuroendocrinology, 27(9), 692-701. https://doi.org/10.1111/jne.12296
Eijo G, et al. Lack of Oestrogenic Inhibition of the Nuclear Factor-κB Pathway in Somatolactotroph Tumour Cells. J Neuroendocrinol. 2015;27(9):692-701. PubMed PMID: 26052658.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Lack of Oestrogenic Inhibition of the Nuclear Factor-κB Pathway in Somatolactotroph Tumour Cells. AU - Eijo,G, AU - Gottardo,M F, AU - Jaita,G, AU - Magri,M L, AU - Moreno Ayala,M, AU - Zárate,S, AU - Candolfi,M, AU - Pisera,D, AU - Seilicovich,A, PY - 2015/01/20/received PY - 2015/04/29/revised PY - 2015/06/01/accepted PY - 2015/6/9/entrez PY - 2015/6/9/pubmed PY - 2016/6/18/medline KW - NF-κB KW - TNF-α KW - apoptosis KW - oestrogens KW - pituitary SP - 692 EP - 701 JF - Journal of neuroendocrinology JO - J Neuroendocrinol VL - 27 IS - 9 N2 - 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. SN - 1365-2826 UR - https://www.unboundmedicine.com/medline/citation/26052658/Lack_of_Oestrogenic_Inhibition_of_the_Nuclear_Factor_κB_Pathway_in_Somatolactotroph_Tumour_Cells_ L2 - https://doi.org/10.1111/jne.12296 DB - PRIME DP - Unbound Medicine ER -