BackgroundCREB3L1 (cAMP-responsive element-binding protein 3-like protein 1), a member of the unfolded protein response, has recently been identified as a metastasis suppressor in both breast and bladder cancer.MethodsQuantitative real time PCR (qPCR) and immunoblotting were used to determine the impact of histone deacetylation and DNA methylation inhibitors on CREB3L1 expression in breast cancer cell lines. Breast cancer cell lines and tumor samples were analyzed similarly, and CREB3L1 gene methylation was determined using sodium bisulfite conversion and DNA sequencing. Immunohistochemistry was used to determine nuclear versus cytoplasmic CREB3L1 protein. Large breast cancer database analyses were carried out to examine relationships between CREB3L1 gene methylation and mRNA expression in addition to CREB3L1 mRNA expression and prognosis.ResultsThis study demonstrates that the low CREB3L1 expression previously seen in highly metastatic breast cancer cell lines is caused in part by epigenetic silencing. Treatment of several highly metastatic breast cancer cell lines that had low CREB3L1 expression with DNA methyltransferase and histone deacetylase inhibitors induced expression of CREB3L1, both mRNA and protein. In human breast tumors, CREB3L1 mRNA expression was upregulated in low and medium-grade tumors, most frequently of the luminal and HER2 amplified subtypes. In contrast, CREB3L1 expression was repressed in high-grade tumors, and its loss was most frequently associated with triple negative breast cancers (TNBCs). Importantly, bioinformatics analyses of tumor databases support these findings, with methylation of the CREB3L1 gene associated with TNBCs, and strongly negatively correlated with CREB3L1 mRNA expression. Decreased CREB3L1 mRNA expression was associated with increased tumor grade and reduced progression-free survival. An immunohistochemistry analysis revealed that low-grade breast tumors frequently had nuclear CREB3L1 protein, in contrast to the high-grade breast tumors in which CREB3L1 was cytoplasmic, suggesting that differential localization may also regulate CREB3L1 effectiveness in metastasis suppression.ConclusionsOur data further strengthens the role for CREB3L1 as a metastasis suppressor in breast cancer and demonstrates that epigenetic silencing is a major regulator of the loss of CREB3L1 expression. We also highlight that CREB3L1 expression is frequently altered in many cancer types suggesting that it could have a broader role in cancer progression and metastasis.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-016-0672-x) contains supplementary material, which is available to authorized users.
The Canadian poultry production industry contributes nearly $10 billion to the Canadian economy and employs nearly 50,000 workers. However, modern poultry facilities are highly contaminated with airborne dust. Although there are many bioaerosols in the poultry barn environment, endotoxin is typically attributed with the negative respiratory symptoms observed in workers. These adverse respiratory symptoms have a higher prevalence in poultry workers compared to workers from other animal confinement buildings. Workers in cage-housed operations compared to floor-housed facilities report a higher prevalence of some respiratory symptoms. We review the current state of knowledge on airborne dust in poultry barns and respiratory dysfunction in poultry workers while highlighting the areas that need further investigation. Our review focuses on the aerobiological pathway of poultry dust including the source and aerosolization of dust and worker exposure and response. Further understanding of the source and aerosolization of dust in poultry operations will aid in the development of management practices to reduce worker exposure and response.
Although bioaerosols from both cage-housed (CH) and floor-housed (FH) poultry operations are highly concentrated, the concentrations of dust, endotoxin, and bacteria are significantly higher in FH bioaerosols. Workers from CH operations have reported a greater prevalence of respiratory symptoms. To date, archaea have been examined in swine and dairy bioaerosols but not in poultry bioaerosols. The objective of this study was to directly compare methanogenic archaea concentrations in bioaerosols from CH and FH poultry facilities. Bioaerosols were collected from 15 CH and 15 FH poultry operations, using stationary area samplers as well as personal sampling devices. Archaea were quantified and their diversity was investigated using polymerase chain reaction (PCR) followed by denaturing gradient gel electrophoresis (DGGE) and band sequencing. Archaea were significantly higher in area and personal bioaerosols of CH poultry operations than in those from FH poultry operations (p < 0.001 and p < 0.05, respectively) and did not differ significantly between area and personal samples within each barn type. Sequences matching Methanobrevibacter woesei, an archaea previously found in poultry samples, were detected in bioaerosol samples from CH operations. Methanogenic archaea concentrations are significantly different between bioaerosols from CH and FH poultry operations.
Most bacteria are more concentrated and most AMR genes are more prevalent in bioaerosols of FH poultry operations, where growth-promoting antibiotics may be used.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.