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: Activation of nuclear factor (NF)-[kappa]B 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)-[alpha] by inhibiting NF-[kappa]B nuclear translocation. In the present study, we examined whether oestrogens also modulate the NF-[kappa]B signalling pathway and apoptosis in GH3 cells, a rat somatolactotroph tumour cell line. As determined by Western blotting, 17[beta]-oestradiol (E2) (10-9 m) increased the nuclear concentration of NF-[kappa]B/p105, p65 and p50 in GH3 cells. However, E2 did not modify the expression of Bcl-xL, a NF-[kappa]B target gene. TNF-[alpha] 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 [mu]m) 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-[alpha]-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 [mu]m). We also analysed the role of the NF-[kappa]B 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-[kappa]B pathway and that the pro-apoptotic effect of TNF-[alpha] on these tumour pituitary cells does not require sensitisation by oestrogens as occurs in normal pituitary cells. NF-[kappa]B was required for the survival of GH3 cells, suggesting that pharmacological inhibition of the NF-[kappa]B pathway could interfere with pituitary tumour progression.

(C) 2015 John Wiley & Sons, Ltd