Emerging functional roles of nuclear receptors in breast cancer

Doan, Tram; Graham, J. Dinny

doi:10.1530/jme-16-0082

Cited by 36 publications

(33 citation statements)

References 189 publications

(198 reference statements)

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“…Links between BC and expression of other NR have already been outlined by our lab and others [5][6][7][8][9][10]. Thyroid hormone receptors (THR) are members of the NR superfamily that mediate the classical genomic actions of thyroid hormone (TH) signaling in numerous tissues and regulate important physiological and developmental processes [11,12].…”

Section: Introductionmentioning

confidence: 96%

Cytoplasmic and Nuclear Forms of Thyroid Hormone Receptor β1 Are Inversely Associated with Survival in Primary Breast Cancer

Shao¹,

Kühn²,

Mayr

et al. 2020

IJMS

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The aim of this study was to investigate the expression of thyroid hormone receptor β1 (THRβ1) by immunohistochemistry in breast cancer (BC) tissues and to correlate the results with clinico-biological parameters. In a well-characterized cohort of 274 primary BC patients, THRβ1 was widely expressed with a predominant nuclear location, although cytoplasmic staining was also frequently observed. Both nuclear and cytoplasmic THRβ1 were correlated with high-risk BC markers such as human epidermal growth factor receptor 2 (HER2), Ki67 (also known as MKI67), prominin-1 (CD133), and N-cadherin. Overall survival analysis demonstrated that cytoplasmic THRβ1 was correlated with favourable survival (p = 0.015), whereas nuclear THRβ1 had a statistically significant correlation with poor outcome (p = 0.038). Interestingly, in our cohort, nuclear and cytoplasmic THRβ1 appeared to be independent markers either for poor (p = 0.0004) or for good (p = 0.048) prognosis, respectively. Altogether, these data indicate that the subcellular expression of THRβ1 may play an important role in oncogenesis. Moreover, the expression of nuclear THRβ1 is a negative outcome marker, which may help to identify high-risk BC subgroups.

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Section: Introductionmentioning

confidence: 96%

Cytoplasmic and Nuclear Forms of Thyroid Hormone Receptor β1 Are Inversely Associated with Survival in Primary Breast Cancer

Shao¹,

Kühn²,

Mayr

et al. 2020

IJMS

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“…There is an emerging role for the ovarian steroid hormone, progesterone, and its receptor, the progesterone receptor (PR), in the development of breast cancer (1–3). Clinical data have shown increased breast cancer incidence in women taking post-menopausal hormone replacement therapy (HRT) whose combined regimens included estrogen and progestins; this increased risk was not present in women taking estrogen-only HRT (4).…”

Section: Introductionmentioning

confidence: 99%

Interferon-Stimulated Genes Are Transcriptionally Repressed by PR in Breast Cancer

Walter

Goodman

Singhal

et al. 2017

Molecular Cancer Research

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The progesterone receptor (PR) regulates transcriptional programs that drive proliferation, survival, and stem cell phenotypes. Although the role of native progesterone in the development of breast cancer remains controversial, PR clearly alters the transcriptome in breast tumors. This study identifies a class of genes, interferon-stimulated genes (ISGs), potently downregulated by ligand-activated PR which have not been previously shown to be regulated by PR. Progestin-dependent transcriptional repression of ISGs was observed in breast cancer cell line models and human breast tumors. Ligand-independent regulation of ISGs was also observed, as basal transcript levels were markedly higher in cells with PR knockdown. PR repressed ISG transcription in response to interferon treatment, the canonical mechanism through which these genes are activated. Liganded PR is robustly recruited to enhancer regions of ISGs, and ISG transcriptional repression is dependent upon PR’s ability to bind DNA. In response to PR activation, key regulatory transcription factors that are required for interferon-activated ISG transcription, STAT2 and IRF9, exhibit impaired recruitment to ISG promoter regions, correlating with PR/ligand-dependent ISG transcriptional repression. Interferon activation is a critical early step in nascent tumor recognition and destruction through immune surveillance. As the large majority of breast tumors are PR-positive at the time of diagnosis, PR-dependent downregulation of interferon signaling may be a mechanism through which early PR-positive breast tumors evade the immune system and develop into clinically relevant tumors. Implications: This study highlights a novel transcriptional mechanism through which PR drives breast cancer development and potentially evades the immune system.

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“…1,2) Current treatment for breast cancer includes surgery, radiotherapy and drug therapy, with drug therapy including hormone therapy, chemotherapy and immunotherapy. 3,4) The pathogenesis of breast cancer has been studied in-depth, 5) and many drugs have emerged for the treatment of breast cancer, with chemotherapy remaining the mainstay of treatment for breast cancer in addition to surgery. In the clinic, the main chemotherapeutic agents used to treat breast cancer include cisplatin and paclitaxel, docetaxel, curcumin, navelbine, and oxaliplatin.…”

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confidence: 99%

Synergistic Activity of an Antimetabolite Drug and Tyrosine Kinase Inhibitors against Breast Cancer Cells

Zhang

Yuan

et al. 2017

Chem. Pharm. Bull.

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Antimetabolite drugs, including the adenosine deaminase inhibitor cladribine, have been shown to induce apoptosis in a variety of cancer cells, and have been widely used in clinical trials of various cancers in conjunction with tyrosine kinase inhibitors (TKIs). Combination treatment with cladribine and gefitinib or dasatinib is expected to have a synergistic inhibitory effect on breast cancer cell growth. Our results demonstrated that the combination treatment had synergistic activity against human breast cancer (MCF-7) cells, enhanced G 2 /M cell arrest and reactive oxygen species (ROS) generation, and increased the loss of mitochondrial membrane potential and cell apoptosis. In addition, the combination treatment decreased Bcl-2 expression. Our results demonstrated that cladribine in combination with gefitinib or dasatinib exerted synergistic anticancer effects on MCF-7 cells by inducing cell cycle arrest, ROS production and apoptosis through the mitochondria-mediated intrinsic pathway.Key words cladribine; gefitinib; dasatinib; breast cancer; combination therapy Breast cancer is the most common malignant tumor and the leading cause of cancer-related deaths in women.1,2) Current treatment for breast cancer includes surgery, radiotherapy and drug therapy, with drug therapy including hormone therapy, chemotherapy and immunotherapy.3,4) The pathogenesis of breast cancer has been studied in-depth, 5) and many drugs have emerged for the treatment of breast cancer, with chemotherapy remaining the mainstay of treatment for breast cancer in addition to surgery. In the clinic, the main chemotherapeutic agents used to treat breast cancer include cisplatin and paclitaxel, docetaxel, curcumin, navelbine, and oxaliplatin. Although these chemotherapy drugs are widely used in the treatment of breast cancer, they often have severe side effects. 6)Recent studies have found that multiple signaling pathways, such as phosphatidylinositol 3-kinase (PI3K) and mitogenactivated protein kinase (MAPK), are involved in breast cancer cell proliferation, and targets of these pathways, such as epidermal growth factor receptor (EGFR), Akt, mammalian target of rapamycin (mTOR), insulin-like growth factor 1 receptor (IGF-1R), human epidermal growth factor receptor-2 (HER2), have become anti-breast cancer drug targets. 7,8) We are known to target anti-breast cancer drugs trastuzumab, lapatinib and so on, but the development of drug resistance in patients has limited their clinical use. With the integration of various disciplines of drug research, the role of multiple targets in biological signaling networks and pathways to achieve appropriate physiological and pathological outcomes has been well studied.9) A growing body of literature has also shown that drug combinations have synergistic anti-cancer effects through the inhibition of these targets. [10][11][12][13][14] In the clinic, combination chemotherapy for breast cancer is widely used, including drugs such as dasatinib and adriamycin, and has shown excellent results. 15)The clinical app...

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Emerging functional roles of nuclear receptors in breast cancer

Cited by 36 publications

References 189 publications

Cytoplasmic and Nuclear Forms of Thyroid Hormone Receptor β1 Are Inversely Associated with Survival in Primary Breast Cancer

Cytoplasmic and Nuclear Forms of Thyroid Hormone Receptor β1 Are Inversely Associated with Survival in Primary Breast Cancer

Interferon-Stimulated Genes Are Transcriptionally Repressed by PR in Breast Cancer

Synergistic Activity of an Antimetabolite Drug and Tyrosine Kinase Inhibitors against Breast Cancer Cells

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