scholarly journals Androgen receptor as potential therapeutic target in metastatic endometrial cancer

Oncotarget ◽  
2016 ◽  
Vol 7 (31) ◽  
pp. 49289-49298 ◽  
Author(s):  
Ingvild Løberg Tangen ◽  
Therese Bredholt Onyango ◽  
Reidun Kopperud ◽  
Anna Berg ◽  
Mari K. Halle ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Androgen Receptor ◽  
Therapeutic Target ◽  
Potential Therapeutic Target

scholarly journals LAMC1 is a prognostic factor and a potential therapeutic target in endometrial cancer

2020 ◽  
Vol 31 (2) ◽  
Author(s):  
Haruko Kunitomi ◽  
Yusuke Kobayashi ◽  
Ren-Chin Wu ◽  
Takashi Takeda ◽  
Eiichiro Tominaga ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Prognostic Factor ◽  
Therapeutic Target ◽  
Potential Therapeutic Target

scholarly journals Plasma membrane proteomics identifies bone marrow stromal antigen 2 as a potential therapeutic target in endometrial cancer

2012 ◽  
Vol 132 (2) ◽  
pp. 472-484 ◽  
Author(s):  
Takuhei Yokoyama ◽  
Takayuki Enomoto ◽  
Satoshi Serada ◽  
Akiko Morimoto ◽  
Shinya Matsuzaki ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Endometrial Cancer ◽  
Plasma Membrane ◽  
Therapeutic Target ◽  
Potential Therapeutic Target ◽  
Membrane Proteomics

Androgen Receptor Is a Potential Therapeutic Target for Bladder Cancer

Urology ◽  
2010 ◽  
Vol 75 (4) ◽  
pp. 820-827 ◽  
Author(s):  
Ji-Tao Wu ◽  
Bang-Min Han ◽  
Sheng-Qiang Yu ◽  
Hui-Ping Wang ◽  
Shu-Jie Xia
Keyword(s):  
Bladder Cancer ◽  
Androgen Receptor ◽  
Therapeutic Target ◽  
Potential Therapeutic Target

scholarly journals CSIG-13. ANDROGEN RECEPTOR IS INVOLVED IN GLIOBLASTOMA AND PRESENTS A POTENTIAL THERAPEUTIC TARGET

2016 ◽  
Vol 18 (suppl_6) ◽  
pp. vi43-vi43 ◽  
Author(s):  
Iris Lavon ◽  
Nomi Zalsman ◽  
Tamar Canello ◽  
Hanna Charbit ◽  
Bracha Zelikovitch ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Therapeutic Target ◽  
Potential Therapeutic Target

scholarly journals Androgen Receptor Is a New Potential Therapeutic Target for the Treatment of Hepatocellular Carcinoma

2008 ◽  
Vol 135 (3) ◽  
pp. 947-955.e5 ◽  
Author(s):  
Weng–Lung Ma ◽  
Cheng–Lung Hsu ◽  
Ming–Heng Wu ◽  
Chun–Te Wu ◽  
Cheng–Chia Wu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Androgen Receptor ◽  
Therapeutic Target ◽  
Potential Therapeutic Target

scholarly journals Androgen Receptor Activation in Glioblastoma Can Be Achieved by Ligand-Independent Signaling through EGFR—A Potential Therapeutic Target

2021 ◽  
Vol 22 (20) ◽  
pp. 10954
Author(s):  
Nomi Zalcman ◽  
Mijal Gutreiman ◽  
Tal Shahar ◽  
Michael Weller ◽  
Iris Lavon
Keyword(s):  
Androgen Receptor ◽  
Mrna Expression ◽  
Therapeutic Target ◽  
Nuclear Translocation ◽  
Kinase Inhibitor ◽  
Receptor Activation ◽  
The Cancer Genome Atlas ◽  
Egfr Signaling ◽  
Akt Inhibitor ◽  
Potential Therapeutic Target

Androgen receptor (AR) is a ligand-mediated transcription factor that belongs to the superfamily of steroid receptors. AR is overexpressed in most glioblastomas and is a potential therapeutic target. In prostate and breast cancers, AR activation can be achieved also by a ligand-independent signaling through receptor tyrosine kinases such as epidermal growth factor receptor (EGFR). Considering its major role in glioblastoma, we explored whether EGFR is involved in AR signaling in this tumor. Analysis of mRNA expression in 28 glioblastoma samples with quantitative real-time reverse-transcription polymerase chain reaction revealed a positive and significant correlation between AR and EGFR mRNA expression levels (R = 0.47, p = 0.0092), which was validated by The Cancer Genome Atlas dataset (n = 671) analysis (R = 0.3, p = 0.00006). Using Western blotting and immunofluorescence staining, we showed that the transduced overexpression of EGFR or its variant EGFRvIII in the U87MG cells induced AR protein overexpression and nuclear translocation and Protein kinase B (AKT) S473 and AR S210/213 phosphorylation. The EGFR kinase inhibitor afatinib and the AKT inhibitor MK2206 reduced AR nuclear translocation. Afatinib diminished AKT phosphorylation at 30 min and 6 h in the EGFR- and EGFRvIII-overexpressing cells, respectively, and decreased AR phosphorylation in EGFR-overexpressing cells at 4 h. Afatinib or MK2206 combination therapy with the AR antagonist enzalutamide in the EGFR and EGFRvIII-overexpressing cells had synergistic efficacy. Our findings suggest that EGFR signaling is involved in AR activation in glioblastoma and buttresses the concept of combining an EGFR signaling inhibitor with AR antagonists as a potential glioblastoma treatment.

scholarly journals Androgen Receptor Could Be a Potential Therapeutic Target in Patients with Advanced Hepatocellular Carcinoma

Cancers ◽  
2017 ◽  
Vol 9 (12) ◽  
pp. 43 ◽  
Author(s):  
Tatsuo Kanda ◽  
Koji Takahashi ◽  
Masato Nakamura ◽  
Shingo Nakamoto ◽  
Shuang Wu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Androgen Receptor ◽  
Therapeutic Target ◽  
Advanced Hepatocellular Carcinoma ◽  
Potential Therapeutic Target

ZMIZ1 Collaborates with NOTCH1 During Induction and Maintenance of T-Cell Acute Lymphoblastic Leukemia

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 75-75
Author(s):  
Lesley A Rakowski ◽  
Derek D Garagiola ◽  
Sarah C Caruso ◽  
Mark Y. Chiang
Keyword(s):  
Gene Expression ◽  
Androgen Receptor ◽  
Acute Lymphoblastic Leukemia ◽  
Cell Lines ◽  
Therapeutic Target ◽  
Lymphoblastic Leukemia ◽  
Ectopic Expression ◽  
Potential Therapeutic Target ◽  
Cell Acute Lymphoblastic Leukemia ◽  
Notch1 Mutations

Abstract Abstract 75 Activating NOTCH1 mutations are found in 40–60% of human T-cell acute lymphoblastic leukemia (T-ALL) samples. In mouse models, most leukemia-associated NOTCH1 mutations fail to induce leukemia. This observation suggests that cooperating oncogenes must be recruited by NOTCH1 to fully induce leukemia. In murine retroviral/transposon insertional mutagenesis screens, induction of the Zmiz1 gene was frequently associated with activation of the Notch1 receptor during leukemogenesis (Uren et al., Cell, 2008; Dupuy et al., Nature, 2005). ZMIZ1 is a transcriptional co-activator of the Protein Inhibitor of Activated STAT-like family that has been implicated for prostate cancer survival. It directly interacts with the androgen receptor to enhance its transcriptional activity. To investigate the role of ZMIZ1 during leukemogenesis, activating NOTCH1 mutations and ZMIZ1 were transduced into hematopoietic progenitor cells. These cells were then used to reconstitute lethally irradiated mice. ZMIZ1 or NOTCH1 alone failed to induce T-ALL after 1 year of observation. In contrast, ZMIZ1 and NOTCH1 in combination induced T-ALL with ∼50% penetrance by 100 days after transplantation. These data show that ZMIZ1 can promote leukemogenesis in cooperation with NOTCH1. To determine the relevance of ZMIZ1 to human leukemia, we screened 15 primary human adult T-ALL samples for ZMIZ1 mRNA and protein. 20% expressed ZMIZ1. In publically available data sets, ZMIZ1 gene expression was significantly enriched by ∼2-fold in early thymocyte precursor ALL (ETP-ALL) samples. The ETP-ALL subgroup comprises about 13% of all T-ALL and may have a highly unfavorable prognosis. We discovered expression of ZMIZ1 in two ETP-like cell lines. To investigate whether ZMIZ1 is a potential therapeutic target, we transduced these cell lines with shRNA directed against ZMIZ1. ZMIZ1 inhibition reduced cell size, increased apoptosis by ∼2-fold, and reduced growth by 75–94%. Furthermore, ZMIZ1 knockdown overcame resistance to NOTCH signaling blockade with g-secretase inhibitors. Since the glucocorticoid receptor is highly homologous to the androgen receptor, we considered the possibility that ZMIZ1 inhibition may promote glucocorticoid resistance. However, we treated ZMIZ1-inhibited T-ALL cell lines with increasing doses of dexamethasone. ZMIZ1-inhibited T-ALL cell lines were twice as sensitive to dexamethasone than uninhibited cells. These data suggest that ZMIZ1 is required for leukemia growth and survival. Inhibition of ZMIZ1 may potentially enhance targeting of T-ALL with NOTCH pathway inhibitors and glucocorticoids. To determine the mechanism underlying ZMIZ1 function, we performed gene expression profiling. We identified C-MYC as a potential downstream target of ZMIZ1. C-MYC is also a direct target of NOTCH1. Ectopic expression of ZMIZ1 or NOTCH1 had weak effects on endogenous C-MYC expression and failed to rescue a C-MYC-dependent T-ALL cell line after withdrawal of ectopic C-MYC. In contrast, ZMIZ1 in combination with NOTCH1 dramatically induced C-MYC expression by ∼7000 fold, induced C-MYC target gene expression, and rescued the C-MYC dependent cell line. ZMIZ1 inhibition lowered C-MYC levels by ∼93%. The interaction between ZMIZ1 and NOTCH appeared to be specific for C-MYC, as modulation of ZMIZ1 levels did not affect the NOTCH1 target genes Hes1, Dtx1, and Cd25. Downregulation of C-MYC partly phenocopied the effects of ZMIZ1 downregulation. However, ectopic expression of C-MYC failed to rescue the growth of ZMIZ1-inhibited cells. These data suggest that C-MYC is an essential but insufficient downstream effector of ZMIZ1 function. In conclusion, ZMIZ1 is new potential therapeutic target in a subset of T-ALL. It functionally interacts with NOTCH1 to promote C-MYC expression and activity. Disclosures: No relevant conflicts of interest to declare.

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