Altered nuclear localization of bax protein in BCNU-resistant glioma cells

被引：19

作者：

Joy, A ^{[1
]}

Panicker, S ^{[1
]}

Shapiro, JR ^{[1
]}

机构：

[1] Barrow Neurol Inst, Lab Neurooncol, Phoenix, AZ 85013 USA

来源：

JOURNAL OF NEURO-ONCOLOGY | 2000年 / 49卷 / 02期

关键词：

apoptosis; chemotherapy resistance; bcl-2; bax; glioma; nucleolus;

D O I：

10.1023/A:1026574123273

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

To investigate the role of apoptosis suppression in glioma chemotherapy resistance, protein levels and subcellular localization of bcl-2 family members were investigated in 2 pairs of sensitive cell lines and their in vitro generated resistant derivatives. The alkylating agent, 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), induced apoptosis in both sensitive cell strains and apoptosis was suppressed in both resistant derivatives. Both resistant cell lines contained altered regulation of a bcl-2 related protein consistent with the suppression of apoptosis. Independent of which bcl-2 family member was dysregulated, resistance was associated with altered regulation in the subcellular localization of bax protein. Following BCNU treatment, bax accumulated in nucleoli and a nuclei containing fraction of sensitive cells but not their resistant derivatives. Nuclear accumulation was an early event in apotosis induction. These data indicates altered subcellular localization of bax may play a role in resistance. In addition, the association between an early, nucleolar localization of bax and the induction of apoptosis suggests that localization of bax to nucleoli may play a role in apoptosis-induction of glioma cells.

引用

页码：117 / 129

页数：13

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