FosB transcription factor regulates COX-2 expression in colorectal cancer cells without affecting PGE2 expression

Cervantes-Madrid, Diana; Nagi, Sabah; Gustafsson, Annika

doi:10.3892/ol.2017.5571

Cited by 17 publications

(15 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Assays for the binding of 3 H-labeled glutamate (PerkinElmer, Stockholm, Sweden) to the MCs (1 × 10 6 cells) were performed in 1.5-ml microcentrifuge tubes using 100 nM 3 H-labeled glutamate (specific activity = 48.6 Ci/mmol) for different incubation periods (5,20,40,60, and 180 min) at 4°C. Incubation in the absence or presence of excess unlabeled glutamate (50 µM) was followed by the addition of 3 H-labeled glutamate.…”

Section: H-glutamate Binding Assaymentioning

confidence: 99%

Glutamate triggers the expression of functional ionotropic and metabotropic glutamate receptors in mast cells

et al. 2020

View full text Add to dashboard Cite

Mast cells are emerging as players in the communication between peripheral nerve endings and cells of the immune system. However, it is not clear the mechanism by which mast cells communicate with peripheral nerves. We previously found that mast cells located within healing tendons can express glutamate receptors, raising the possibility that mast cells may be sensitive to glutamate signaling. To evaluate this hypothesis, we stimulated primary mast cells with glutamate and showed that glutamate induced the profound upregulation of a panel of glutamate receptors of both the ionotropic type (NMDAR1, NMDAR2A, and NMDAR2B) and the metabotropic type (mGluR2 and mGluR7) at both the mRNA and protein levels. The binding of glutamate to glutamate receptors on the mast cell surface was confirmed. Further, glutamate had extensive effects on gene expression in the mast cells, including the upregulation of proinflammatory components such as IL-6 and CCL2. Glutamate also induced the upregulation of transcription factors, including Egr2, Egr3 and, in particular, FosB. The extensive induction of FosB was confirmed by immunofluorescence assessment. Glutamate receptor antagonists abrogated the responses of the mast cells to glutamate, supporting the supposition of a functional glutamate-glutamate receptor axis in mast cells. Finally, we provide in vivo evidence supporting a functional glutamate-glutamate receptor axis in the mast cells of injured tendons. Together, these findings establish glutamate as an effector of mast cell function, thereby introducing a novel principle for how cells in the immune system can communicate with nerve cells.

show abstract

Section: H-glutamate Binding Assaymentioning

confidence: 99%

Glutamate triggers the expression of functional ionotropic and metabotropic glutamate receptors in mast cells

et al. 2020

View full text Add to dashboard Cite

show abstract

“…The three top up and down regulated genes in the CLOs vs primary cell lines were TFF3, PLEKHB1, LTB and FOSB, CAV1, AHNAK2, respectively. Interestingly, FOSB is a proto-oncogene, and CAV1 expression has been linked with mammary tumorigenesis and increased lung metastasis 47,48 . AHNAK2 has also previously been found to be upregulated in PDAC 49 .…”

Section: Discussionmentioning

confidence: 99%

“…This dedifferentiation theory is supported by a previous study which has shown that when implanted orthotopically, organoids recapitulate tumour progression from precursor PanIn lesions to metastatic carcinoma 25 . Interestingly, genes down regulated in PDX tumour/organoids and CLOs include genes which have increased expression in cancers, including potential PDAC biomarkers (CYR61, PLAU, FOSB, ECM1, LIF, GJB3 and CAV1) 48,49,[57][58][59][60][61][62] . There is also an increased expression of tumour suppressor genes LRIG1 and SEMA3F 55,63 .…”

Section: Discussionmentioning

confidence: 99%

Modelling of pancreatic cancer biology: transcriptomic signature for 3D PDX-derived organoids and primary cell line organoid development

Nelson

Zhang

Roche

et al. 2020

Sci Rep

View full text Add to dashboard Cite

With a five-year survival rate of 9%, pancreatic ductal adenocarcinoma (PDAC) is the deadliest of all cancers. The rapid mortality makes PDAC difficult to research, and inspires a resolve to create reliable, tractable cellular models for preclinical cancer research. Organoids are increasingly used to model PDAC as they maintain the differentiation status, molecular and genomic signatures of the original tumour. In this paper, we present novel methodologies and experimental approaches to develop PDAC organoids from PDX tumours, and the simultaneous development of matched primary cell lines. Moreover, we also present a method of recapitulating primary cell line cultures to organoids (CLOs). We highlight the usefulness of CLOs as PDAC organoid models, as they maintain similar transcriptomic signatures as their matched patient-derived organoids and patient derived xenografts (PDX)s. These models provide a manageable, expandable in vitro resource for downstream applications such as high throughput screening, functional genomics, and tumour microenvironment studies. With a rapid progression and fatal outcome, pancreatic cancer is one of the deadliest of all cancers. Long-term survivors are limited to those with resected early stage tumours; however, overall survival rate is a dismal 9%, with a median survival time of 7-11 months 1,2. As pancreatic cancer is notoriously asymptomatic at an early stage, 80% of patients are diagnosed after the cancer has metastasised, making them ineligible for resection, which is the only curative treatment. The number of cases of pancreatic cancer has been steadily rising since 2004 3. It is currently the fourth most common cause of cancer death in the US, and by 2030 it is estimated that it will surpass breast and colorectal cancer to become the second most common cause of death by cancer 4. The majority of pancreatic cancers are in the exocrine pancreas (95%) known as pancreatic ductal adenocarcinoma (PDAC), and 5% are in the endocrine pancreas 5. The leading epidemiological factors include smoking, obesity, type II diabetes mellitus and acute pancreatitis, which account for approximately 25% of PDAC cases 6-9. A limitation in the understanding of the disease progression and development of effective treatments in PDAC may be due the lack of in vitro patient tumour representative models. Established 2D cell lines are the most widely used model for the development and testing of chemotherapeutics for over 50 years 10. The ability of cell lines to grow indefinitely makes them a low-cost, repeatable model, easy to manipulate and are an important base for discovery and proof-of-concept studies. Their importance in cancer research is indisputable, however, their use as a robust clinical model is questionable 11. During passaging, cell lines undergo genetic modifications, such as copy number variation and point mutations 12. Cell lines also have a high level of homogeneity, which does not represent the heterogenetic nature of PDAC tumours, and not all cancer subtypes are well represented as t...

show abstract

“…Cyclooxygenase (COX)-2 plays crucial roles in the metabolism of arachidonic acid to PGE2. Therefore, COX-2 is well known to be positively associated with carcinogenesis, malignant aggressiveness, and poor outcomes in many types of malignancies [7][8][9] . However, pathological activities of PGE2 are not always dependent on COX-2 because various other factors besides COX-2 regulate PGE2 production 10,11 .…”

Section: Introductionmentioning

confidence: 99%

“…On the other hand, we should know the facts that the binding of PGE2 to its speci c receptor, E-prostanoid receptor (EP), is essential to exsert pathophysiological functions of PGE2 [14]. The EP receptor family consists of four isoforms (EP1-4 receptor), and the interactions between PGE2 and EP receptors in malignancies vary depending on cell type and tumor-surrounding conditions 5,7,15,16 .…”

Section: Introductionmentioning

confidence: 99%

Oral administration of E-type prostanoid (EP) 1 receptor antagonist suppresses carcinogenesis and development of prostate cancer via upregulation of apoptosis in an animal model

Miyata

Masato

Mitsunari

et al. 2021

Preprint

View full text Add to dashboard Cite

Prostaglandin E2 plays important roles in carcinogenesis and malignant potential of prostate cancer (PC) by binding to its specific receptors, E-type prostanoid (EP) receptors. However, anti-carcinogenic effects of EP receptor antagonist are not clear. In this study, feed with or without EP1 receptor antagonist were given to a mouse model of prostate cancer. The mice were sacrificed at 10, 15, 30, and 52 weeks of age. Apoptosis was evaluated by immunohistochemical analysis using cleaved caspase-3. The incidence of cancer in the experimental group was significantly lower than that in the control group at 15, 30, and 52 weeks of age. The percentage of poorly differentiated PC cells was significantly lower in the experimental group than in the control group at 30 and 52 weeks of age. The survival period in the experimental group was significantly longer than that in the control group, and the percentage of apoptotic cells in the experimental group was significantly higher than that in the control group at 15, 30, and 52 weeks of age. Thus, an EP1 receptor antagonist delayed PC progression via the upregulation of apoptosis. We suggest that EP1 receptor may be a novel chemopreventive agent for the development of PC.

show abstract

FosB transcription factor regulates COX-2 expression in colorectal cancer cells without affecting PGE2 expression

Cited by 17 publications

References 28 publications

Glutamate triggers the expression of functional ionotropic and metabotropic glutamate receptors in mast cells

Glutamate triggers the expression of functional ionotropic and metabotropic glutamate receptors in mast cells

Modelling of pancreatic cancer biology: transcriptomic signature for 3D PDX-derived organoids and primary cell line organoid development

Oral administration of E-type prostanoid (EP) 1 receptor antagonist suppresses carcinogenesis and development of prostate cancer via upregulation of apoptosis in an animal model

Contact Info

Product

Resources

About