Interleukin-7 induces apoptosis of 697 pre-B cells expressing dominant-negative forms of STAT5: evidence for caspase-dependent and -independent mechanisms

Olivia Lanvin , Fabrice Gouilleux , Catherine Mullié , Cécile Mazière (1) , Vincent Fuentes , Eliane Bissac , Françoise Dantin , Jean-Claude Maziere (1) , Aline Regnier , Kaiss Lassoued , Valérie Gouilleux-Gruart

1 CHU Amiens-Picardie

The transcription factors STAT5A and STAT5B (STAT: signal transducer and activator of transcription) play a major role in the signaling events elicited by a number of growth factor and cytokine receptors. In this work, we aimed to investigate the role of STAT5 in human precursor B cell survival by introducing dominant-negative (DN) forms of STAT5A or STAT5B in the 697 pre-B cell line. All clones expressing DN forms of either transcription factor exhibited a higher spontaneous apoptotic rate that was massively enhanced upon interleukin-7 (IL-7) stimulation. This was associated with caspase 8 cleavage, mitochondrial transmembrane potential disruption and caspase 3 activation. However, the DN forms of STAT5 did not alter the expression of Bcl-2, Bax, Bcl-x, Bim, A1 and Mcl1 proteins in IL-7-stimulated cells. The pancaspase inhibitor Z-Val-Ala-Asp-fluoromylmethyl ketone partially suppressed IL-7-mediated mitochondrial transmembrane potential disruption and cell death, suggesting that IL-7 induced the death of DN STAT5 expressing 697 cells through caspase-dependent and -independent mechanisms that both require mitochondrial activation.

Domains: Life Sciences [q-bio]

Olivia Lanvin, Fabrice Gouilleux, Catherine Mullié, Cécile Mazière, Vincent Fuentes, et al.. Interleukin-7 induces apoptosis of 697 pre-B cells expressing dominant-negative forms of STAT5: evidence for caspase-dependent and -independent mechanisms. Oncogene, 2004, 23 (17), pp.3040-3047. ⟨10.1038/sj.onc.1207450⟩. ⟨hal-02425322⟩