Epiregulin: Roles in normal physiology and cancer

Riese, David J.; Cullum, Richard L.

doi:10.1016/j.semcdb.2014.03.005

Cited by 149 publications

(169 citation statements)

References 98 publications

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“…Overexpressed EREG has been linked to dysregulation of mitogen-activated protein kinase signaling via the EGF pathway as well as the ERBB pathway, and this overexpression in the sensitive cells may reflect an underlying drive toward the mitogen-activated protein kinase/ERBB pathways. 54,55 Conversely, in the arginase-resistant cells, overexpression of the heat shock protein HSPA6 was demonstrated, suggesting that this may be a mechanism by which these cells attain resistance, especially in light of the finding that HSP inhibition is cytotoxic to AML. 56 EREG and EGFR signaling, as well as the heat shock protein family, play key roles in solid tumor cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

Arginine dependence of acute myeloid leukemia blast proliferation: a novel therapeutic target

Mussai

Egan

Higginbotham-Jones

et al. 2015

Blood

139

153

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Key Points• Arginase depletion with BCT-100 pegylated recombinant human arginase is cytotoxic to AML blasts.Acute myeloid leukemia (AML) is one of the most common acute leukemias in adults and children, yet significant numbers of patients relapse and die of disease. In this study, we identify the dependence of AML blasts on arginine for proliferation. We show that AML blasts constitutively express the arginine transporters CAT-1 and CAT-2B, and that the majority of newly diagnosed patients' blasts have deficiencies in the arginine-recycling pathway enzymes argininosuccinate synthase and ornithine transcarbamylase, making them arginine auxotrophic. BCT-100, a pegylated human recombinant arginase, leads to a rapid depletion in extracellular and intracellular arginine concentrations, resulting in arrest of AML blast proliferation and a reduction in AML engraftment in vivo. BCT-100 as a single agent causes significant death of AML blasts from adults and children, and acts synergistically in combination with cytarabine. Using RNA sequencing, 20 further candidate genes which correlated with resistance have been identified. Thus, AML blasts are dependent on arginine for survival and proliferation, as well as depletion of arginine with BCT-100 of clinical value in the treatment of AML. (Blood. 2015;125(15):2386-2396

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Section: Discussionmentioning

confidence: 99%

Arginine dependence of acute myeloid leukemia blast proliferation: a novel therapeutic target

Mussai

Egan

Higginbotham-Jones

et al. 2015

Blood

139

153

View full text Add to dashboard Cite

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“…Epiregulin, a 46-amino acid protein that belongs to the EGF family, binds to the EGF receptor and ERBB4 (HER4), and can stimulate signaling of ERBB3 (HER2/neu) and ERBB3 (HER3). Deregulated epiregulin activity was noted in a variety of cancers, including breast, lung, colon, stomach, bladder, head and neck, and liver, and epiregulin normally regulates ovarian follicle formation and oocyte development 27 . In this report, epiregulin was downregulated after BPA exposure.…”

Section: Discussionmentioning

confidence: 99%

Gene expression analysis of uterine smooth muscle cells exposed to bisphenol A

Kang

Song

Cho

2014

Toxicol. Environ. Health Sci.

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To evaluate the effect of bisphenol A (BPA) on gene expression changes in uterine myometrium, uterine smooth muscle cells were incubated with 2.28 ng/mL BPA for 48 h. Total RNA was extracted and quantified spectrophotometrically. Gene expression changes were analyzed using oligonucleotide microarray hybridization comparing the treated and control groups (1.5-fold change, p⁄ ⁄0.05). Data indicated that 560 genes were upregulated and 231 were downregulated in response to BPA exposure. The biological processes positively associated with gene upregulation included the regulation of cell differentiation, cellular metabolic processes, cell proliferation and smooth muscle contraction. In contrast, genes involved in mitosis, lipid metabolism, regulation of muscle cell differentiation and cell adhesion were significantly downregulated. In the KEGG pathway analysis, MAPK signaling pathway, insulin signaling pathway and extracellular matrix (ECM)-mediated interactions were positively associated with gene upregulation. Results Gene Expression Profiles Induced by BPA in Uterine Smooth Muscle CellGene expression changes were analyzed by comparing the treated and control groups using statistical criteria (1.5-fold change, p⁄0.05). Three independent samples were analyzed. Results indicated that 560 genes were upregulated in response to BPA exposure and 231 were downregulated.The 560 upregulated and 231 downregulated genes were classified according to the GO terms of biological processes and KEGG pathway analysis, to investigate the molecular mechanisms related to BPA exposure. EASE analysis (http://david.abcc.ncifcrf.gov/) was also performed. The key biological processes that were significantly affected (Fisher's exact test, p⁄

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“…Studies have confirmed that curcumin exerts wide-range anti-tumor activities [9]. Curcumin is shown to inhibit cancer cell survival and proliferation, to induce cancer cell death and apoptosis, and to suppress cancer-related angiogenesis [9].…”

Section: Introductionmentioning

confidence: 99%

“…Curcumin, or 1,7-bis(4-hydroxy-3methoxyphenyl)-1,6-heptadien-3,5-dione, is the main bioactive component of turmeri from the rhizome of Curcuma longa [9]. Studies have confirmed that curcumin exerts wide-range anti-tumor activities [9].…”

Section: Introductionmentioning

confidence: 99%