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Peroxisome proliferator-activated receptor gamma and BRCA1.

ABSTRACT: Peroxisome proliferator-activated receptor gamma agonists have been proposed as breast cancer preventives. Individuals who carry a mutated copy of BRCA1, DNA repair-associated gene, are at increased risk for development of breast cancer. Published data in the field suggest there could be interactions between peroxisome proliferator-activated receptor gamma and BRCA1 that could influence the activity of peroxisome proliferator-activated receptor gamma agonists for prevention. This review explores these possible interactions between peroxisome proliferator-activated receptor gamma, peroxisome proliferator-activated receptor gamma agonists and BRCA1 and discusses feasible experimental directions to provide more definitive information on the potential connections.

SUBMITTER: Furth PA

PROVIDER: S-EPMC6494719 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Peroxisome proliferator-activated receptor gamma and BRCA1.

Furth Priscilla A PA

Endocrine-related cancer 20190201 2

Peroxisome proliferator-activated receptor gamma agonists have been proposed as breast cancer preventives. Individuals who carry a mutated copy of BRCA1, DNA repair-associated gene, are at increased risk for development of breast cancer. Published data in the field suggest there could be interactions between peroxisome proliferator-activated receptor gamma and BRCA1 that could influence the activity of peroxisome proliferator-activated receptor gamma agonists for prevention. This review explores ...[more]

PMID: 30444720

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Project description:BackgroundBRCA1 mutated breast cancers are commonly diagnosed as negative for classical hormone receptors i.e. estrogen receptor, progesterone receptor and/or Her2. Due to these common targets being absent the application of anti-endocrine therapies is rather limited and a certain focus has been set on discovering alternative target molecules. We recently highlighted thyroid hormone receptors (TRs) to predict prognosis in breast cancer patients that had been diagnosed a BRCA1 germline mutation. Vitamin D Receptor (VDR), Retinoid X Receptor (RXR) and Peroxisome Proliferator-activated Receptor γ (PPARγ) are known to interact with TRs by forming functional heterodimers. Whether VDR, RXR or PPARγ are expressed in BRCA1 mutated breast cancer or may even be present in case of triple negativity is not known. Hence the current study aimed to investigate VDR, RXR and PPARγ in BRCA1 mut breast cancer and to test whether any of the three may be associated with clinico-pathological criteria including overall survival.MethodsThis study analyzed VDR, RXR and PPARγ by immunohistochemistry in BRCA1 associated (n = 38) and sporadic breast cancer (n = 79). Receptors were quantified by applying an established scoring system (IR-score) and were tested for association with clinico-pathological variables.ResultsVDR, RXR and PPARγ were detected in over 90% of triple negative BRCA1 mut breast cancer and were significantly (VDR: p < 0.001, RXR: p = 0.010, PPARγ: p < 0.001) overexpressed in BRCA1 mutated as compared to sporadic cancer cases. VDR and RXR positivity predicted prolonged overall survival only in BRCA1 mutated cases while such association was not observed in sporadic breast cancer.ConclusionsIn conclusion, this is the first study to describe VDR, RXR and PPARγ in BRCA1 mutated breast cancer. Based on the data presented here these receptors may be hypothesized to potentially evolve as interesting markers or even targets in hereditary breast cancer. However, independent studies are indispensable thus to confirm this hypothesis.

Dataset Information

Peroxisome proliferator-activated receptor gamma and BRCA1.

Publications

Peroxisome proliferator-activated receptor gamma and BRCA1.

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