Epoxyeicosatrienoic acid (EET) production via cytochrome P450 (CYP) epoxygenases closely correlates with the progression of breast cancer. However, its role in the development of chemoresistant breast cancers has yet to be elucidated. Here, we found that CYP3A4 expression and its epoxy-product, 11,12-epoxyeicosatrienoic acid (11,12-EET) was enhanced in tamoxifen (TAM)-resistant MCF-7 (TAMR-MCF-7) breast cancer cells compared to control MCF-7 cells. Treatment of TAMR-MCF-7 cells with ketoconazole and azamulin (selective CYP3A4 inhibitors) or 14,15-epoxyeicosa-5(Z)-enoic acid (14,15-EEZE, an EET antagonist) inhibited cellular proliferation and recovered the sensitivity to 4-hydroxytamoxifen. Chick chorioallantoic membrane and trans-well migration analyses revealed that the enhanced angiogenic, tumorigenic, and migration intensities of TAMR-MCF-7 cells were also significantly suppressed by ketoconazole and 14,15-EEZE. We previously reported that Pin1, a peptidyl prolyl isomerase, is a crucial regulator for higher angiogenesis and epithelial-mesenchymal transition characteristics of TAMR-MCF-7 cells. EET inhibition suppressed E2F1-dependent Pin1 gene transcription, and Pin1 silencing also blocked cell proliferation, angiogenesis, and migration of TAMR-MCF-7 cells. Our findings suggest that the CYP3A4-mediated EET pathway represents a potential therapeutic target for the treatment of tamoxifen-resistant breast cancer.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5642617 | PMC |
| http://dx.doi.org/10.18632/oncotarget.20329 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
GradeDiff-IM: An Ensembles Model-based Grade Classification of Breast Cancer.
Biomed Phys Eng Express
January 2025
School of Engineering and Computing, University of the West of Scotland, University of the West of Scotland - Paisley Campus, Paisley PA1 2BE, UK, City, Paisley, PA1 2BE, UNITED KINGDOM OF GREAT BRITAIN AND NORTHERN IRELAND.
Cancer grade classification is a challenging task identified from the cell structure of healthy and abnormal tissues. The partitioner learns about the malignant cell through the grading and plans the treatment strategy accordingly. A major portion of researchers used DL models for grade classification.
View Article and Find Full Text PDFUnveiling Sociocultural Barriers to Breast Cancer Awareness Among the South Asian Population: Case Study of Bangladesh and West Bengal, India.
JMIR Hum Factors
January 2025
New College of Florida, Sarasota, FL, United States.
Background: Bangladesh and West Bengal, India, are 2 densely populated South Asian neighboring regions with many socioeconomic and cultural similarities. In dealing with breast cancer (BC)-related issues, statistics show that people from these regions are having similar problems and fates. According to the Global Cancer Statistics 2020 and 2012 reports, for BC (particularly female BC), the age-standardized incidence rate is approximately 22 to 25 per 100,000 people, and the age-standardized mortality rate is approximately 11 to 13 per 100,000 for these areas.
View Article and Find Full Text PDFFASN inhibition shows the potential for enhancing radiotherapy outcomes by targeting glycolysis, AKT, and ERK pathways in breast cancer.
Int J Radiat Biol
January 2025
Department of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, Taipei City, Taiwan.
Purpose: Breast cancer ranks as the most prevalent cancer in women, characterized by heightened fatty acid synthesis and glycolytic activity. Fatty acid synthase (FASN) is prominently expressed in breast cancer cells, regulating fatty acid synthesis, thereby enhancing tumor growth and migration, and leading to radioresistance. This study aims to investigate how FASN inhibition affects cell proliferation, migration, and radioresistance in breast cancer, as well as the mechanisms involved.
View Article and Find Full Text PDFPreliminary characterisation of the spatial immune and vascular environment in triple negative basal breast carcinomas using multiplex fluorescent immunohistochemistry.
PLoS One
January 2025
Department of Pathology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
Triple negative breast cancers often contain higher numbers of tumour-infiltrating lymphocytes compared with other breast cancer subtypes, with their number correlating with prolonged survival. Since little is known about tumour-infiltrating lymphocyte trafficking in triple negative breast cancers, we investigated the relationship between tumour-infiltrating lymphocytes and the vascular compartment to better understand the immune tumour microenvironment in this aggressive cancer type. We aimed to identify mechanisms and signaling pathways responsible for immune cell trafficking in triple negative breast cancers, specifically of basal type, that could potentially be manipulated to change such tumours from immune "cold" to "hot" thereby increasing the likelihood of successful immunotherapy in this challenging patient population.
View Article and Find Full Text PDFFractional and stochastic modeling of breast cancer progression with real data validation.
PLoS One
January 2025
Biology Department, Faculty of Science, Islamic University of Madinah, Madinah, Saudi Arabia.
This study presents a novel approach to modeling breast cancer dynamics, one of the most significant health threats to women worldwide. Utilizing a piecewise mathematical framework, we incorporate both deterministic and stochastic elements of cancer progression. The model is divided into three distinct phases: (1) initial growth, characterized by a constant-order Caputo proportional operator (CPC), (2) intermediate growth, modeled by a variable-order CPC, and (3) advanced stages, capturing stochastic fluctuations in cancer cell populations using a stochastic operator.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!