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PPARgamma activation by thiazolidinediones (TZDs) may modulate breast carcinoma outcome: the importance of interplay with TGFbeta signalling.

Jarrar MH, Baranova A - J. Cell. Mol. Med. (2007 Jan-Feb)

Bottom Line: The thiazolidinediones (TZDs) are a class of synthetic antidiabetic drugs exerting its action primarily upon activation of the peroxisome proliferator-activated receptor-gamma (PPARgamma).Another layer of complexity arises at the later stages of tumour development, when TGFbeta acts as a tumour promoter: its overexpression is associated with poor prognosis, higher degree of tumour vascularization and metastasis.In this review, we dissect possible interplays between chronic exposure of breast tis-sue to TZDs and TGFbeta signalling and predict influence of TZD exposure on cancer-related clinical outcome.

View Article: PubMed Central - PubMed

Affiliation: Center for Biomedical Genomics and Bioinformatics, Molecular and Microbiology Department, College of Science, George Mason University, Fairfax, VA, USA.

ABSTRACT
The thiazolidinediones (TZDs) are a class of synthetic antidiabetic drugs exerting its action primarily upon activation of the peroxisome proliferator-activated receptor-gamma (PPARgamma). 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 PPARgamma by TZDs interferes with oestrogen receptor signalling, STAT5B and NF-kappaB signalling cascades. On the other hand, TZDs repress TGFbeta 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 TGFbeta 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 TGFbeta signalling and predict influence of TZD exposure on cancer-related clinical outcome.

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TZDs activate PPAR signalling that interferes with OR, STAT5B, TFGβ and NF-κB pathways. Most likely, this interference is mutual.
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getmorefigures.php?uid=PMC4401221&req=5

fig01: TZDs activate PPAR signalling that interferes with OR, STAT5B, TFGβ and NF-κB pathways. Most likely, this interference is mutual.

Mentions: PPARγ interferes with numerous cellular pathways, particularly OR, STAT5B, TFGβ and NF-κB. Most likely, the interference is mutual, as it is exerted through shared molecular components taking part in the propagation of the signal or the transcriptional regulation (Fig. 1).


PPARgamma activation by thiazolidinediones (TZDs) may modulate breast carcinoma outcome: the importance of interplay with TGFbeta signalling.

Jarrar MH, Baranova A - J. Cell. Mol. Med. (2007 Jan-Feb)

TZDs activate PPAR signalling that interferes with OR, STAT5B, TFGβ and NF-κB pathways. Most likely, this interference is mutual.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4401221&req=5

fig01: TZDs activate PPAR signalling that interferes with OR, STAT5B, TFGβ and NF-κB pathways. Most likely, this interference is mutual.
Mentions: PPARγ interferes with numerous cellular pathways, particularly OR, STAT5B, TFGβ and NF-κB. Most likely, the interference is mutual, as it is exerted through shared molecular components taking part in the propagation of the signal or the transcriptional regulation (Fig. 1).

Bottom Line: The thiazolidinediones (TZDs) are a class of synthetic antidiabetic drugs exerting its action primarily upon activation of the peroxisome proliferator-activated receptor-gamma (PPARgamma).Another layer of complexity arises at the later stages of tumour development, when TGFbeta acts as a tumour promoter: its overexpression is associated with poor prognosis, higher degree of tumour vascularization and metastasis.In this review, we dissect possible interplays between chronic exposure of breast tis-sue to TZDs and TGFbeta signalling and predict influence of TZD exposure on cancer-related clinical outcome.

View Article: PubMed Central - PubMed

Affiliation: Center for Biomedical Genomics and Bioinformatics, Molecular and Microbiology Department, College of Science, George Mason University, Fairfax, VA, USA.

ABSTRACT
The thiazolidinediones (TZDs) are a class of synthetic antidiabetic drugs exerting its action primarily upon activation of the peroxisome proliferator-activated receptor-gamma (PPARgamma). 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 PPARgamma by TZDs interferes with oestrogen receptor signalling, STAT5B and NF-kappaB signalling cascades. On the other hand, TZDs repress TGFbeta 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 TGFbeta 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 TGFbeta signalling and predict influence of TZD exposure on cancer-related clinical outcome.

Show MeSH
Related in: MedlinePlus