Heat shock proteins in breast cancer progression--a suitable case for treatment?
Heat shock proteins in breast cancer progression--a suitable case for treatment?
复制标题
乳腺癌进展中的热休克蛋白 - 适合治疗的病例？
DOI：
10.3109/02656736.2010.490254
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Calderwood SK
中科院分区：
文献类型：
--
作者：
Calderwood SK
热休克蛋白（HSP）和热休克因子1 （HSF1）是热休克反应（HSR）的关键因子，与乳腺癌的病因有关。在乳腺细胞转化过程中，至少有两个HSP家族成员Hsp27和Hsp70的细胞浓度显著升高。这些变化导致热休克蛋白通过阻断细胞凋亡和复制性衰老途径介导的肿瘤细胞失活抑制。因此，热休克蛋白的增加介导了癌症的两种常见特征，并有利于细胞出生而不是细胞死亡。此外，Hsp90通过稳定乳腺肿瘤中发现的突变和过表达的癌蛋白来促进转化，并允许在缺乏生长因子的情况下激活生长刺激和转化途径。HSF1似乎在乳腺癌中扮演着类似的促进转化的角色。因此，在乳腺癌细胞中诱导HSR的某些方面导致生长刺激并抑制细胞死亡。因此，HSP和HSF1的药理学靶向是必要的，在Hsp90的情况下，抑制药物正在进行治疗乳腺癌和其他癌症的临床试验。
Heat shock proteins (HSP) and heat shock factor 1 (HSF1), key factors in the heat shock response (HSR) have been implicated in the etiology of breast cancer. At least two members of the HSP family, Hsp27 and Hsp70 undergo significant increases in cellular concentration during the transformation of mammary cells. These changes result in HSP-mediated inhibition of tumor cell inactivation through blockade of the apoptosis and replicative senescence pathways. The increases in HSP thus mediate two of the common hallmarks of cancer and favor cell birth over cell death. In addition, Hsp90 plays a role in facilitating transformation by stabilizing the mutated and overexpressed oncoproteins found in breast tumors, and permitting the activation of growth stimulatory and transforming pathways in the absence of growth factors. HSF1 appears to play a similar role as a facilitator of transformation in mammary carcinoma. Induction of some facets of the HSR in breast cancer cells therefore leads to growth stimulation and inhibits cell death. Pharmacological targeting of HSP and HSF1 is therefore indicated and in the case of Hsp90, inhibitory drugs are undergoing clinical trial for treatment of breast carcinoma and other cancers.
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影响因子：
3.1
作者：
Calderwood, Stuart K.;Ciocca, Daniel R.
通讯作者：
Ciocca, Daniel R.
影响因子：
64.5
作者：
Dai, Chengkai;Whitesell, Luke;Lindquist, Susan
通讯作者：
Lindquist, Susan
影响因子：
8
作者：
Khaleque, MA;Bharti, A;Calderwood, SK
通讯作者：
Calderwood, SK
影响因子：
11.2
作者：
Kawabe M;Mandic M;Taylor JL;Vasquez CA;Wesa AK;Neckers LM;Storkus WJ
通讯作者：
Storkus WJ
影响因子：
3.4
作者：
Neckers, Len;Ivy, S. Percy
通讯作者：
Ivy, S. Percy