Rapid modulation of the apoptosis regulatory genes, bcl-2 and bax by prolactin in rat Nb2 lymphoma cells

被引:91
作者
Leff, MA
Buckley, DJ
Krumenacker, JS
Reed, JC
Miyashita, T
Buckley, AR
机构
[1] UNIV N DAKOTA, SCH MED, DEPT PHARMACOL & TOXICOL, GRAND FORKS, ND 58202 USA
[2] BURNHAM INST, CANC RES CTR, LA JOLLA, CA 92037 USA
关键词
D O I
10.1210/en.137.12.5456
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The Nb2 rat lymphoma represents a useful model for investigation of molecular events coupled to PRL-induced proliferation. Moreover, recent evidence has also demonstrated the utility of this system to study mechanisms linked to programmed cell death (apoptosis). Thus, glucocorticosteroids activate apoptosis in lactogen-dependent Nb2 cells, whereas the addition of PRL abrogates this effect. The present study was conducted to determine whether PRL stimulation in lactogen-dependent Nb2-11 or autonomous Nb2-SFJCD1 cultures alters expression of bcl-2 or bax, genes that suppress or facilitate apoptosis, respectively. We demonstrate that PRL stimulation in stationary Nb2-11 cultures significantly increased the level of bcl-2 messenger RNA (mRNA) within 3 h (15-fold) and its protein product by 6 h, time points previously shown to correspond with G(1) cell cycle progression. In Nb2-SFJCD1 cells, bcl-2 mRNA was found to be constitutively present. Addition of PRL to these lactogen-independent cultures further enhanced its expression at the mRNA and protein levels with a kinetic pattern similar to that observed in the PRL-dependent Line. Results from stability studies indicated that increased bcl-2 mRNA evoked by PRL in Nb2 cell lines was most likely not attributable to increased stability ofits transcripts. Furthermore, the rapid increase in its expression in PRL-stimulated Nb2-11 cells was not altered by inhibition of protein synthesis suggesting a direct action of the hormone. PRL also increased bax mRNA by 8 h in Nb2-11 cultures. However, hormone stimulation markedly attenuated the level of the Bax protein from 2-6 h. In contrast, bax expression in Nb2-SFJCD1 cultures remained unaltered by the addition of the hormone. These results demonstrate that altered expression of bcl-2 and bax are each associated with PRL-stimulated cell cycle progression in Nb2 cells. Moreover, bcl-2 appears to be an immediate-early gene induced by PRL in the hormone-dependent line and may represent an important regulator of early G(1) cell cycle progression most likely by suppressing cell death mechanisms.
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收藏
页码:5456 / 5462
页数:7
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