Lack of oestrogenic inhibition of the NF-κB Pathway in somatolactotroph tumour cells.

GUADALUPE EIJO; MARIA FLORENCIA GOTTARDO; GABRIELA JAITA; MARIA LAURA MAGRI; MARIELA MORENO AYALA; SANDRA ZARATE; MARIANELA CANDOLFI; DANIEL PISERA; ADRIANA SEILICOVICH

JOURNAL OF NEUROENDOCRINOLOGY.

WILEY-BLACKWELL PUBLISHING, INC

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

0953-8194

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