PPARgamma activation by thiazolidinediones (TZDs) may modulate breast carcinoma outcome: the importance of interplay with TGFbeta signalling.
PPARgamma activation by thiazolidinediones (TZDs) may modulate breast carcinoma outcome: the importance of interplay with TGFbeta signalling.
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DOI：
10.1111/j.1582-4934.2007.00003.x
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发表时间：
2007-01
影响因子：
5.3
通讯作者：
Baranova A
中科院分区：
文献类型：
--
作者：
Jarrar MH;Baranova A
噻唑烷二酮类(TZD)是一类人工合成的抗糖尿病药物，主要作用于激活过氧化物酶体增殖物激活受体γ(PPARγ)。鉴于II型糖尿病的广泛发病率以及这些患者终生暴露于TZD，TZD的长期治疗有可能改变其他常见人类疾病的临床表型，例如乳腺癌。有证据表明，TZDS作为乳腺癌抑制剂，至少在体外和动物模型中是这样。TZDS刺激PPARγ干扰雌激素受体信号转导、STAT5B和NF-κB信号转导。另一方面，TZD抑制转化生长因子β信号，这是众所周知的乳腺癌发展初期阶段的抑制因子。当转化生长因子β作为肿瘤促进剂时，另一层复杂性出现在肿瘤发展的后期：它的过度表达与不良预后、较高的肿瘤血管化程度和转移有关。需要对长期服用TZD的患者进行乳腺癌的纵向研究。在这篇综述中，我们剖析了乳腺组织慢性暴露于TZDS和转化生长因子β信号之间可能的相互作用，并预测了TZD暴露对癌症相关临床结果的影响。
The thiazolidinediones (TZDs) are a class of synthetic antidiabetic drugs exerting its action primarily upon acti-vation of the peroxisome proliferator-activated receptor-γ (PPARγ). Given the widespread incidence of diabetes type II and lifelong exposure of these patients to TZDs, there is a possibility that chronic treatment with TZD modifies clinical phenotypes of other common human diseases, for example breast carcinoma. There is evidence that TZDs act as breast carcinoma suppression agents, at least in the in vitro and animal models. Stimulation of the PPARγ by TZDs interferes with oestrogen receptor signalling, STAT5B and NF-κB signalling cascades. On the other hand, TZDs repress TGFβ signalling, a well-known suppressor of the initial stages of breast carcinoma development. Another layer of complexity arises at the later stages of tumour development, when TGFβ acts as a tumour promoter: its overexpression is associated with poor prognosis, higher degree of tumour vascularization and metastasis. Longitudinal studies of breast carcinoma development in chronic TZD users are needed. In this review, we dissect possible interplays between chronic exposure of breast tis-sue to TZDs and TGFβ signalling and predict influence of TZD exposure on cancer-related clinical outcome.
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影响因子：
6.4
作者：
Badawi, AF;Badr, MZ
通讯作者：
Badr, MZ
DOI：
10.1073/pnas.95.15.8806
发表时间：
1998-07-21
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
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作者：
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作者：
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DOI：
10.1073/pnas.0403621101
发表时间：
2004-07-06
影响因子：
11.1
作者：
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通讯作者：
Iglehart, JD