Lack of oestrogenic inhibition of the NF-kappaB pathway in pituitary tumour cells

G. EIJO; M.F.GOTTARDO; G. JAITA; M.L.MAGRI; M. MORENO AYALA; S. ZARATE; M.CANDOLFI; D. PISERA; A. SEILICOVICH

JOURNAL OF NEUROENDOCRINOLOGY.

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2015 vol. 27 p. 692 - 701

0953-8194

Activation of NF-kappaB promotes cell proliferation and inhibits apoptosis. We have previously shown that oestrogens sensitise normal anterior pituitary cells to the apoptotic effect of TNF-alpha by inhibiting NF-kappaB nuclear translocation. In the present report we examined whether oestrogens also modulate NF-kappaB signalling pathway and apoptosis in GH3 cells, a rat somatolactotroph tumour cell line. As determined by Western blot, 17beta-oestradiol (E2, 10-9 M) increased nuclear concentration of NF-kappaB/p105, p65 and p50 in GH3 cells. However, E2 did not modify expression of Bcl-xL, a NF-kappaB target gene. TNF-alpha induced apoptosis of GH3 cells incubated in either presence or absence of E2. BAY 11-7082 (BAY, 5 µM), Inhibition of the NF-kappaB pathway using BAY 11-7082 (BAY) decreased viability of GH3 cells and increased the percentage of TUNEL-positive GH3 cells. BAYalso increased TNF-alpha-induced apoptosis of GH3 cells, an effect that was further increased by an inhibitor of the JNK pathway, SP 600125 (10 µM). We also analysed the role of NF-kappaB 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 NF-kappaB pathway and that the pro-apoptotic effect of TNF-alpha on these tumour pituitary cells does not require sensitisation by oestrogens as happens in normal pituitary cells. NF-kappaB was required for survival of GH3 cells suggesting that pharmacological inhibition of NF-κB pathway could interfere with pituitary tumour progression.