Artemin is oncogenic for human mammary carcinoma cells

Kang, Jian; Perry, Jo K.; Pandey, Vijay; Fielder, Graeme C.; Mei, Bin; Qian, Pengxu; Wu, ZS; Zhu, Tao; Li, Dongxu; Lobie, Peter E.

doi:10.1038/onc.2009.66

Cited by 72 publications

(120 citation statements)

References 37 publications

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“…in vivo, we implanted MCF7-Vec or MCF7-ARTN cells into the mammary fat pad of immunodeficient mice, which were randomized to receive estrogen supplement combined with either tamoxifen or vehicle. As shown in Figure 4a, in mice supplemented with estrogen, tumors formed by MCF7-ARTN cells were 1.5-fold larger than those formed by MCF7-Vec cells, in confirmation of previously reported data (Kang et al, 2009). Tamoxifen inhibited the growth of tumors derived from MCF7-Vec cells as expected (Sarkaria et al, 1993).…”

Section: Artn Enhanced Er Transcriptional Activity and Functionsupporting

confidence: 90%

“…In the absence of antiestrogen treatment, forced expression of ARTN in MCF-7 cells did not affect cell number in monolayer culture as described previously (Kang et al, 2009;Figure 3a). However, in the presence of either tamoxifen or fulvestrant, MCF7-ARTN cells showed an increase in cell number compared with MCF7-Vec cells ( Figure 3a).…”

Section: Artn Enhanced Er Transcriptional Activity and Functionmentioning

confidence: 64%

“…BrdU incorporation and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assays were performed on tumor sections to quantify proliferation and apoptosis within the tumor at the time of termination of the experiment. As previously described (Kang et al, 2009) Forced expression of ARTN reduced ERb expression and increased BCL-2 expression in mammary carcinoma cells We next determined whether ARTN-induced antiestrogen resistance is due to modification of ER expression. We therefore compared ERa and ERb protein levels in MCF7-Vec and MCF7-ARTN cells.…”

Section: Artn Enhanced Er Transcriptional Activity and Functionmentioning

confidence: 91%

“…ARTN signaling is mediated through a multi-component receptor complex including the glycosylphosphatidylinositol-anchored GDNF family receptor a3 (GFRa3) or GFRa1 as one ligand binding component and RET receptor tyrosine kinase as one common signaling component (Airaksinen and Saarma, 2002;Carmillo et al, 2005). We have recently identified an oncogenic role of ARTN in mammary carcinoma (Kang et al, 2009). ARTN protein was detectable in 65% of mammary carcinoma and correlated to decreased overall survival (OAS) of breast cancer patients.…”

Section: Introductionmentioning

confidence: 99%

“…Forced expression of ARTN in mammary carcinoma cells promoted anchorage-independent growth and enhanced migration and invasion, with resultant increased tumor growth in vivo. In addition, analysis of the cancer microarray database Oncomine revealed a significant association of ARTN expression with residual disease after chemotherapy (Kang et al, 2009). Boulay et al (2008) have recently reported the induction of RET and GFRa1 expression by estrogen treatment in ER-positive mammary carcinoma cells, indicating that GFL signaling may interact with estrogen signaling and potentially mediate some of the cellular functions of estrogen.…”

Section: Introductionmentioning

confidence: 99%

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Artemin is estrogen regulated and mediates antiestrogen resistance in mammary carcinoma

et al. 2010

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We have previously identified an oncogenic role of artemin (ARTN), a member of glial cell derived neurotrophic factor family of ligands, in mammary carcinoma. We herein report that ARTN is an estrogen-inducible gene. Metaanalysis of gene expression data sets showed that ARTN expression is positively correlated to estrogen receptor (ER) status in human mammary carcinoma. Furthermore, in patients with ER-positive mammary carcinoma treated with tamoxifen, high ARTN expression is significantly correlated with decreased survival. Forced expression of ARTN in ER-positive human mammary carcinoma cells increased ER transcriptional activity, promoted estrogenindependent growth and produced resistance to tamoxifen and fulvestrant in vitro and to tamoxifen in xenograft models. ARTN-stimulated resistance to tamoxifen and fulvestrant is mediated by increased BCL-2 expression. Conversely, depletion of endogenous ARTN by smallinterfering RNA or functional antagonism of ARTN by antibody enhanced the efficacy of antiestrogens. Tamoxifen decreased ARTN expression in tamoxifen-sensitive mammary carcinoma cells whereas ARTN expression was increased in tamoxifen-resistant cells and not affected by tamoxifen treatment. Antibody inhibition of ARTN in tamoxifen-resistant cells improved tamoxifen sensitivity. Functional antagonism of ARTN therefore warrants consideration as an adjuvant therapy to enhance antiestrogen efficacy in ER-positive mammary carcinoma.

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Section: Artn Enhanced Er Transcriptional Activity and Functionsupporting

confidence: 90%

Section: Artn Enhanced Er Transcriptional Activity and Functionmentioning

confidence: 64%

Section: Artn Enhanced Er Transcriptional Activity and Functionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Artemin is estrogen regulated and mediates antiestrogen resistance in mammary carcinoma

et al. 2010

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RET, a targetable driver of pancreatic adenocarcinoma

Amit

Na’ara

Fridman

et al. 2019

Intl Journal of Cancer

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Pancreatic ductal adenocarcinoma (PDA) remains a deadly disease, affecting about 40,000 individuals in the United States annually. We aimed to characterize the role of RET as a co‐driver of pancreas tumorigenesis. To assess the role of RET as a co‐driver of PDA, we generated a novel triple mutant transgenic mouse based on the cre‐activated p53R172H gene and a constitutively active RET M919T mutant (PRC). Survival analysis was performed using Kaplan–Meier analysis. Study of human PDA specimens and Pdx‐1‐Cre/KrasG12D /p53R172H (KPC) mice revealed that RET is upregulated during pancreas tumorigenesis, from inception through precursor lesions, to invasive cancer. We demonstrated that activation of RET is capable of inducing invasive pancreatic carcinomas in the background of the P53 inactivation mutation. Compared to KPC mice, PRC animals had distinct phenotypes, including longer latency to tumor progression, longer survival, and the presence of multiple macrometastases. Enhanced activation of the MAPK pathway was observed as early as the PanIN 2 stage. Sequencing of the exonic regions of KRAS in PRC‐derived PDA cells revealed no evidence of KRAS mutations. RET can be an essential co‐driver of pancreatic tumorigenesis in conjugation with KRAS activity. These data suggest that RET may be a potential target in the treatment of PDA.

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ELTD1 is present in extracellular vesicles derived from endothelial cells as a cleaved extracellular domain which induces in vivo angiogenesis

Sheldon

Zhang

Bridges

et al. 2022

J of Extracellular Bio

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ELTD1/ADGRL4 is an adhesion GPCR with an important role in angiogenesis. We recently identified a role for ELTD1 in wound repair and inflammation. Activation of ELTD1 in endothelial cells results in a type II EMT to myofibroblast-like cells that have enhanced angiogenic ability. Furthermore, expression of Eltd1 in murine breast cancer cells increases tumour growth by increasing blood vessel size and perfusion and by creating an immunosuppressive microenvironment. As extracellular vesicles (EVs) are known to be involved in vascular development, growth and maturation we investigated the composition and functional effects of the EVs isolated from ELTD1 expressing cells to elucidate their role in these processes. A highly glycosylated form of the extracellular domain (ECD) of ELTD1 is readily incorporated into EVs. Using mass spectrometry-based proteomics we identified proteins that are enriched in ELTD1-EVs and are involved in haemostasis and immune responses. ELTD1 enriched EVs were pro-angiogenic in vivo and in vitro and the presence of the ECD alone induced endothelial sprouting. In endothelial cells experiencing laminar flow, ELTD1 levels were reduced in the EVs when they are quiescent, showing a relationship between ELTD1 and the activation state of the endothelium. Using FACS, we detected a significant increase in vesicular ELTD1 in the plasma of patients with preeclampsia, a condition characterized by endothelial dysfunction. These data confirm a role for ELTD1 in wound repair and inflammation and reveal its potential as a biomarker of vessel dysfunction.

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Artemin is oncogenic for human mammary carcinoma cells

Cited by 72 publications

References 37 publications

Artemin is estrogen regulated and mediates antiestrogen resistance in mammary carcinoma

Artemin is estrogen regulated and mediates antiestrogen resistance in mammary carcinoma

RET, a targetable driver of pancreatic adenocarcinoma

ELTD1 is present in extracellular vesicles derived from endothelial cells as a cleaved extracellular domain which induces in vivo angiogenesis

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