Induction of heat shock proteins by heregulin β1 leads to protection from apoptosis and anchorage-independent growth
Induction of heat shock proteins by heregulin β1 leads to protection from apoptosis and anchorage-independent growth
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DOI：
10.1038/sj.onc.1208798
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发表时间：
2005-09-01
期刊：
影响因子：
8
通讯作者：
Calderwood, SK
中科院分区：
文献类型：
--
作者：
Khaleque, MA;Bharti, A;Calderwood, SK
热休克蛋白（HSP）水平的升高在癌症中广泛存在，并预示着预后不良和对治疗的抵抗。我们发现肿瘤细胞中HSP的升高可以由高度恶性的调蛋白β 1（HRG β 1）诱导，该因子通过热休克转录因子1（HSF 1）诱导HSP表达。hsf 1基因的失活阻止了HRG β 1对HSP的诱导。HSP表达通过HRG β 1与细胞表面c-erbB受体结合引发的级联反应诱导，并导致细胞内HSF 1拮抗剂糖原合成酶激酶3的抑制。通过该途径激活的HSF 1在保护细胞免于凋亡和通过HRGb 1介导锚定非依赖性生长中起关键作用，表明HSF 1在该致瘤途径中的作用。
Elevation of heat shock protein (HSP) levels is widespread in cancer and predicts a poor prognosis and resistance to therapy. We show that HSP elevation in tumor cells can be induced by the highly malignant factor heregulin beta 1 (HRG beta 1), which induces HSP expression through heat shock transcription factor 1 (HSF1). Inactivation of the hsf1 gene prevents HSP induction by HRG beta 1. HSP expression is induced through a cascade response initiated by HRG beta 1 binding to c-erbB receptors on the cell surface and which leads to the inhibition of intracellular HSF1 antagonist glycogen synthase kinase 3. HSF1 activated by this pathway plays a key role in the protection of cells from apoptosis and the mediation of anchorage independent growth by HRGb1, indicating a role for HSF1 in this tumorigenic pathway.