Butyrate-induced reversal of dexamethasone resistance in autonomous rat Nb2 lymphoma cells.
The parental rat Nb2 lymphoma is a prolactin (PRL)-dependent T cell line. Exposure of a PRL-independent subline, Nb2-SFJCD1, to sodium butyrate (NaBT) causes transient reversal of their growth factor-independent proliferation in association with constitutive expression of protooncogenes pim-1 and c-myc. In the present study, we investigated the effect of NaBT treatment on the sensitivity of Nb2-SFJCD1 cells to dexamethasone (DEX)-induced apoptosis. Pretreatment with NaBT (2 mM, 72 h) partially reversed resistance to apoptosis in Nb2-SFJCD1 cells exposed to DEX (100 nM) for 12 h, assessed by flow cytometric analyses of DNA fragmentation. However, the cytolytic effect of DEX was abrogated by PRL in a time- and concentration-dependent manner. Evaluation of apoptosis-associated gene expression in NaBT-pre-treated cultures incubated with DEX or DEX+PRL indicated that the apoptosis resistance did not stem from altered bcl-2 or bax expression. However, there was a strong correlation between the resistance to DEX-activated apoptosis and their enhanced expression of pim-1 mRNA and protein. The results show that it is possible to reverse DEX-induced apoptosis of Nb2 pre-T cells and suggest the pim-1 gene product has an important role as a suppressor of this process, perhaps functioning as a mediator of PRL action.
Buckley
A R
AR
Department of Pharmacology and Toxicology, University of North Dakota School of Medicine and Health Sciences, Grand Forks 58202-9037, USA. abuckley@mail.med.und.nodak.edu
Krumenacker
J S
JS
Buckley
D J
DJ
Leff
M A
MA
Magnuson
N S
NS
Reed
J C
JC
Miyashita
T
T
de Jong
G
G
Gout
P W
PW