Prohibitin promotes androgen receptor activation in ER-positive breast cancer

Liu, Pengying; Xu, Yumei; Zhang, Wenwen; Li, Yan; Tang, Lin; Chen, Weiwei; Xu, Jianping; Sun, Qiang; Guan, Xiaoxiang

doi:10.1080/15384101.2017.1295193

Cited by 20 publications

(12 citation statements)

References 31 publications

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“…Upon BRCA1 interference, we found a reduced level of prohibitin, coherently with literature data that highlighted the ability of prohibitin in inhibiting breast cancer cell proliferation and promoting apoptosis [33]. In addition, we found a reduced level of gelsolin, fully in agreement with what we previously published [20].…”

Section: Discussionsupporting

confidence: 92%

2D Gel Electrophoresis to Address Biological Issues

Scumaci¹,

Cuda²

2019

Proteomics Technologies and Applications

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Two-dimensional (2D) gel electrophoresis is a high-resolution technique for the study of proteome. This chapter describes how it can be applied to characterize specific differences in the proteome profile of breast cancer cells following gene target interference. The proteome is the complete set of proteins encoded by a genome, and proteomic analysis consists in profiling the whole proteins expressed in a given cell, tissue, organ, or organism. Proteomic expression has the main purpose of qualitatively and quantitatively comparing proteins expressed under physiological and/or pathological conditions. Although it is not the unique approach used in modern proteomics, two-dimensional electrophoresis (2DE) is unrivaled allowing simultaneous separation of thousands of proteins and the detection of posttranslational modification, not predictable through genome analysis. 2DE combines two physical principles to separate complex protein mixtures: the isoelectric point and the molecular weight. The result is a gel map in which each protein isoform present in the sample can be visualized as a spot, analyzed, quantified, and identified by mass spectrometry analysis. Here we outline features and advantages of the 2DE-based proteomic approach and we describe how 2DE meets biochemistry and molecular biology to address specific issues.

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Section: Discussionsupporting

confidence: 92%

2D Gel Electrophoresis to Address Biological Issues

Scumaci¹,

Cuda²

2019

Proteomics Technologies and Applications

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“…Since the original identification of PHB1 as a proliferation suppressor in rat liver cells 1 , the effect of PHB1 on cancer proliferation has been studied. Some studies found that PHB1 inhibits breast cancer cell proliferation by up-regulating androgen receptor (AR) expression in estrogen receptor (ER)-positive breast cancer cells 15 , 63 . PHB1 also inhibits proliferation of human osteosarcoma MG-63 cells by interacting with tumor suppressors such as p53 64 .…”

Section: Role Of Phb1 and Phb2 In Tumorigenesismentioning

confidence: 99%

Significance of prohibitin domain family in tumorigenesis and its implication in cancer diagnosis and treatment

Yang

2018

Cell Death Dis

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Prohibitin (PHB) was originally isolated and characterized as an anti-proliferative gene in rat liver. The evolutionarily conserved PHB gene encodes two human protein isoforms with molecular weights of ~33 kDa, PHB1 and PHB2. PHB1 and PHB2 belong to the prohibitin domain family, and both are widely distributed in different cellular compartments such as the mitochondria, nucleus, and cell membrane. Most studies have confirmed differential expression of PHB1 and PHB2 in cancers compared to corresponding normal tissues. Furthermore, studies verified that PHB1 and PHB2 are involved in the biological processes of tumorigenesis, including cancer cell proliferation, apoptosis, and metastasis. Two small molecule inhibitors, Rocaglamide (RocA) and fluorizoline, derived from medicinal plants, were demonstrated to interact directly with PHB1 and thus inhibit the interaction of PHB with Raf-1, impeding Raf-1/ERK signaling cascades and significantly suppressing cancer cell metastasis. In addition, a short peptide ERAP and a natural product xanthohumol were shown to target PHB2 directly and prohibit cancer progression in estrogen-dependent cancers. As more efficient biomarkers and targets are urgently needed for cancer diagnosis and treatment, here we summarize the functional role of prohibitin domain family proteins, focusing on PHB1 and PHB2 in tumorigenesis and cancer development, with the expectation that targeting the prohibitin domain family will offer more clues for cancer therapy.

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“…It has been reported that AR is expressed in 60-70% of ER À BC and in approximately 68% of the cases in this research. 26,27 The AR signalling pathway has a significant role in the proliferation and survival of ER À BCs, and inhibition of AR has a therapeutic value in in-vitro and in-vivo models of ER À AR + BC cells. 28 PDEF was first identified as an AR co-regulator and an activator of prostate-specific antigen (PSA) in the prostate.…”

Section: S U R V I V a L A N A L Y S I Smentioning

confidence: 99%

Clinical significance of PDEF factor expression and its relation to androgen receptor in ER⁻ breast cancer

Cao

et al. 2018

Histopathology

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Aims The mechanism of androgen receptor (AR) promoting tumour growth in oestrogen receptor‐negative (ER−) breast cancer (BC) is undetermined. Prostate‐derived ETS factor (PDEF) is highly restricted to the hormone‐regulated tissues of epithelial cells, such as those in the prostate, breast and other tissues. It has been demonstrated that PDEF expression is associated with AR in prostate cancer. In this research, we aimed to investigate the relationship between PDEF and AR in ER− BC. Methods and results We immunohistochemically evaluated the correlation between PDEF and AR expression in 246 cases of ER− invasive BC, and investigated their relationship in ER− BC cell lines. The expression of PDEF was associated with the positive expression of AR (P < 0.001) and a worse survival rate (P = 0.006). PDEF+ tumours were significantly more often AR+ (P < 0.001). AR and PDEF were more often co‐expressed and the series of AR+PDEF+ (126 of 246, 51.2%) had a poor survival rate (P = 0.046). In Cox models, PDEF expression (P = 0.028) was an independent predictor for overall survival (OS). At the cellular protein and mRNA levels, our experiments also showed a statistically significant positive correlation between PDEF and AR, and that PDEF may be regulated by AR. Conclusions PDEF is associated with markers of bad prognosis, supporting its role as a growth promoter in ER− BC. Our findings also provide evidence that PDEF is strongly correlated with AR expression in ER− breast cancer; it may be a downstream target gene of AR and a potential prognostic factor in ER− BC.

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Prohibitin promotes androgen receptor activation in ER-positive breast cancer

Cited by 20 publications

References 31 publications

2D Gel Electrophoresis to Address Biological Issues

2D Gel Electrophoresis to Address Biological Issues

Significance of prohibitin domain family in tumorigenesis and its implication in cancer diagnosis and treatment

Clinical significance of PDEF factor expression and its relation to androgen receptor in ER⁻ breast cancer

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Prohibitin promotes androgen receptor activation in ER-positive breast cancer

Cited by 20 publications

References 31 publications

2D Gel Electrophoresis to Address Biological Issues

2D Gel Electrophoresis to Address Biological Issues

Significance of prohibitin domain family in tumorigenesis and its implication in cancer diagnosis and treatment

Clinical significance of PDEF factor expression and its relation to androgen receptor in ER− breast cancer

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Clinical significance of PDEF factor expression and its relation to androgen receptor in ER⁻ breast cancer