The breast cancer-associated gene-1 (BRCA1) plays many important functions in multiple biological processes/pathways. Mice homozygous for a targeted deletion of full-length BRCA1 (Brca1Delta11/Delta11) display both increased tumorigenesis and premature aging, yet molecular mechanisms underlying these defects remain elusive. Here, we show that Brca1 deficiency leads to increased expression of several insulin-like growth factor (IGF) signaling axis members in multiple experimental systems, including BRCA1-deficient mice, primary mammary tumors, and cultured human cells. Furthermore, we provide evidence that activation of IGF signaling by BRCA1 deficiency can also occur in a p53-independent fashion. Our data indicate that BRCA1 interacts with the IRS-1 promoter and inhibits its activity that is associated with epigenetic modification of histone H3 and histone H4 to a transcriptional repression chromatin configuration. We further show that BRCA1-deficient mammary tumor cells exhibit high levels of IRS-1, and acute suppression of Irs-1 using RNA interference significantly inhibits growth of these cells. Those observations provide a molecular insight in understanding both fundamental and therapeutic BRCA1-associated tumorigenesis and aging.
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http://dx.doi.org/10.1158/0008-5472.CAN-05-4570 | DOI Listing |
Methods Cell Biol
January 2025
Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Department of Microbiology, Immunology and Infectious Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Arnie Charbonneau Cancer Research Institute, Calgary, AB, Canada. Electronic address:
Breast cancer is the most common cancer in women and continues to have a significant impact in cancer-associated deaths worldwide. Investigating the complex roles of infiltrating immune subsets within the tumor microenvironment (TME) will enable a better understanding of disease progression and reveal novel therapeutic strategies for patients with breast cancer. The mammary-specific expression of polyomavirus middle T oncoprotein (MMTV-PyMT) was first established in 1992 by William Muller and is the most commonly used genetically engineered mouse model (GEMM) for breast cancer research.
View Article and Find Full Text PDFMol Cell Endocrinol
January 2025
Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing 211166, China. Electronic address:
Bisphenol A (BPA), a commonly used plastic additive, is believed to cause obesity. As an environmental endocrine disruptor, BPA is closely associated with the onset and progression of BC. However, the molecular mechanisms underlying the promotion of breast cancer by BPA remain unclear.
View Article and Find Full Text PDFJ Neurol
January 2025
Second Department of Neurology, Attikon University Hospital, National & Kapodistrian University of Athens, Athens, Greece.
Introduction: The current literature on the prevalence and potential association between disease-modifying therapies (DMTs) and cancer risk in the MS population has yielded mixed findings.
Methods: This study aimed to estimate cancer prevalence and cancer risk in patients with MS (PwMS) under prolonged DMT exposure. Database search include: MEDLINE PUBMED, SCOPUS, and Google Scholar.
Anal Chem
January 2025
Center for Advanced Analytical Science, Guangzhou Key Laboratory of Sensing Materials and Devices, Guangdong Engineering Technology Research Center for Sensing Materials and Devices, School of Chemistry and Chemical Engineering, Guangzhou University, Guangzhou 510006, P. R. China.
The screening of glycoprotein markers has become an integral part of the in vitro diagnosis of malignant tumors. Herein, an electrochemical method based on alkaline phosphatase (ALP)-mediated enzymatic silver deposition is reported for the highly sensitive detection of glycoprotein tumor markers, in which ALP enzymes are decorated to the glycan moieties of targets via the lectin-carbohydrate interactions. As glycoproteins are conjugated with multiple glycan chains, lectin-mediated labeling can result in the decoration of each target with multiple ALP enzymes.
View Article and Find Full Text PDFClin Nucl Med
January 2025
From the Nuclear Medicine.
PET/CT targeting fibroblast activation protein α (FAP) in cancer-associated fibroblasts shows promise in theranostics. Here, we report the case of a 31-year-old woman with hormone receptor-positive/human epidermal growth factor receptor 2-negative breast cancer who presented with rising CA15-3 for further diagnostic workup. Whereas [18F]FDG PET/CT was unremarkable, novel [68Ga]RTX-1363 PET/CT revealed intense tracer accumulation in thoracoabdominal lymph nodes and both ovaries.
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