A novel association between the human heat shock transcription factor 1 (HSF1) and prostate adenocarcinoma

A novel association between the human heat shock transcription factor 1 (HSF1) and prostate adenocarcinoma
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DOI:
10.1016/s0002-9440(10)64954-1
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发表时间:
2000-03-01
影响因子:
6
通讯作者:
Roy-Burman, P
Roy-Burman, P
中科院分区:
医学2区
文献类型:
--
作者:
Hoang, AT;Huang, JP;Roy-Burman, P

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在一对非转移性(PC-3)和转移性变异(PC-3M)人前列腺癌细胞系中寻找差异表达基因,发现人类热休克因子(HSF1)是PC-3M细胞中过表达的基因产物。对原发性前列腺癌标本的分析表明,相对于正常前列腺细胞,HSF1在大多数恶性前列腺上皮细胞中普遍上调。在已知的HSF1作用效应中,HSP70和HSP90的组成水平不会因PC-SM细胞中HSF1的自然表达升高或PC-3细胞中HSF1的转导过表达而显著改变。然而,在这两种情况下,HSP27的基础水平都持续增加了两到三倍。在对热休克的反应中,高基础浓度的HSP90在这些细胞中没有进一步增强,HSP70无论HSF1水平如何都上调,而当HSF1上调时,除了HSF1的表达已经过高外,HSP27也会升高。这些结果首次证明HSF1在人类前列腺癌细胞中过度表达,至少在前列腺癌细胞中有一个结果。HSP27是细胞生长、分化或凋亡的重要因子。
A search for differentially expressed genes in a pair of nonmetastatic (PC-3) versus metastatic variant (PC-3M) human prostate carcinoma cell lines led to identification of the human heat shock factor (HSF1) as an overexpressed gene product in PC-3M tells. Analysis of primary prostate cancer specimens indicated that HSF1 is generally up-regulated in most of the malignant prostate epithelial cells relative to the normal prostate cells. Among the known effecters of HSF1 action, constitutive levels of HSP70 and HSP90 are not significantly altered by the naturally elevated expression of HSF1 as in PC-SM cells or by transduced overexpression of HSF1 in PC-3 cells. The basal levels of HSP27 in both cases are, however, consistently increased by two- to threefold. With respect to response to heat shock, high basal concentration of HSP90 is not further enhanced in these cells, and HSP70 is up-regulated irrespective of HSF1 level Heat shock, however, causes an increase in HSP27 when HSF1 is up-regulated, except when the expression of HSF1 is already too high. These results document for the first time that HSF1 is overexpressed in human prostate cancer cells, at least one consequence of which in the prostate cancer cell. lines tested is stimulation of both basal and stress-induced expression of HSP27, an important factor in cell growth, differentiation, or apoptosis.