A5016741414- Cancer Cells and Metastasis
- BRCA gene mutations in cancer
- Cancer Genomics and Diagnostics
- Gene expression and cancer classification
- NF-κB Signaling Pathways
- Advanced Breast Cancer Therapies
- Single-cell and spatial transcriptomics
- HER2/EGFR in Cancer Research
- Monoclonal and Polyclonal Antibodies Research
- Estrogen and related hormone effects
- PI3K/AKT/mTOR signaling in cancer
- Muscle Physiology and Disorders
- Cytokine Signaling Pathways and Interactions
- Nutrition, Genetics, and Disease
- Circular RNAs in diseases
- Lung Cancer Treatments and Mutations
- MicroRNA in disease regulation
- Natural product bioactivities and synthesis
- RNA modifications and cancer
- Digestive system and related health
- Epigenetics and DNA Methylation
- Metastasis and carcinoma case studies
- Breast Cancer Treatment Studies
- Cell Image Analysis Techniques
- RNA Research and Splicing
Indiana University School of Medicine
2016-2025
Indiana University – Purdue University Indianapolis
2016-2025
University of Indianapolis
2020-2024
Indiana University
2014-2024
University School
2023
Indiana University Indianapolis
2020
Indiana University Bloomington
2010
Walther Cancer Foundation
2003-2006
Collège de France
1996
Inserm
1996
Abstract Introduction A subpopulation (CD44 + /CD24 - ) of breast cancer cells has been reported to have stem/progenitor cell properties. The aim this study was investigate whether the unique ability invade, home, and proliferate at sites metastasis. Methods CD44 CD24 expression determined by flow cytometry. Northern blotting used determine proinvasive 'bone lung metastasis signature' genes. matrigel invasion assay intracardiac inoculation into nude mice were evaluate invasion, homing...
Estrogen receptors (ERs) mediate most of the biological effects estrogen in mammary and uterine epithelial cells by binding to response elements promoter region target genes or through protein-protein interactions. Anti-estrogens such as tamoxifen inhibit growth ER-positive breast cancers reducing expression estrogen-regulated genes. However, anti-estrogen-resistant tumors remains a significant clinical problem. Here we show that phosphatidylinositol (PI) 3-kinase AKT activate ERalpha...
Breast cancers often progress from a hormone-dependent, nonmetastatic, antiestrogen-sensitive phenotype to hormone-independent, antiestrogen- and chemotherapy-resistant with highly invasive metastatic growth properties. This progression is usually accompanied by altered function of the estrogen receptor (ER) or outgrowth ER-negative cancer cells. To understand molecular mechanisms responsible for breast cancers, activities transcription factor NF-kappaB (which modulates expression genes...
Metastasis of cancer cells is a complex process involving multiple steps including invasion, angiogenesis, and trafficking through blood vessels, extravasations, organ-specific homing, growth. While matrix metalloproteinases, urokinase-type plasminogen activator, cytokines play major role in invasion chemokines such as stromal derived factor-1α (SDF-1α) their receptors CXCR4 are thought to critical motility, proliferation at specific metastatic sites. We others have previously reported that...
Estradiol (E2) regulates gene expression at the transcriptional level by functioning as a ligand for estrogen receptor alpha (ERα) and beta (ERβ). E2-inducible proteins c-Myc E2Fs are required optimal ERα activity secondary responses, respectively. We show that E2 induces 21 microRNAs represses seven in MCF-7 breast cancer cells; these have potential to control 420 E2-regulated 757 non-E2-regulated mRNAs post-transcriptional level. The serine/threonine kinase, AKT, alters of microRNAs....
Breast cancer cells with CD44+/CD24- cell surface marker expression profile are proposed as stem (CSCs). Normal breast epithelial that express higher levels of stem/progenitor associated genes. We, amongst others, have shown undergone to mesenchymal transition (EMT) display the phenotype. However, whether all genes induce EMT confer phenotype is unknown. We hypothesized only a subset generates cells. MCF-10A cells, subpopulation which spontaneously acquire phenotype, were used identify...
Cancer stem-like cells are thought to contribute tumor recurrence. The anthrax toxin receptor 1 (ANTXR1) has been identified as a functional biomarker of normal stem and breast cancer cells. Primary cell-enriched basal (CD49f(+)/EpCAM(-)/Lin(-)) expressed higher levels ANTXR1 compared with mature luminal CD49f(+)/EpCAM(-), CD44(+)/EpCAM(-), CD44(+)/CD24(-), or ALDEFLUOR-positive subpopulations were enriched for expression. CD44(+)/CD24(-)/ANTXR1(+) displayed enhanced self-renewal measured by...
RNA Binding Proteins (RBPs) are a class of post-transcriptional regulatory molecules which increasingly documented to be dysfunctional in cancer genomes. However, our current understanding these alterations is limited. Here, we delineate the mutational landscape ∼1300 RBPs ∼6000 Our analysis revealed that have an average ∼3 mutations per Mb across 26 types. We identified 281 enriched for (GEMs) at least one type. GEM were found undergo frequent frameshift and inframe deletions as well...
Single-cell RNA sequencing (scRNA-seq) is an evolving technology used to elucidate the cellular architecture of adult organs. Previous scRNA-seq on breast tissue utilized reduction mammoplasty samples, which are often histologically abnormal. We report a rapid collection/processing protocol perform biopsies healthy women and identify 23 epithelial cell clusters. Putative cell-of-origin signatures derived from these clusters applied analyze transcriptomes ~3,000 cancers. Gene mature luminal...
Abstract Purpose: The transcription factor nuclear factor-κB (NF-κB) promotes the production of angiogenic, antiapoptotic, and prometastatic factors that are involved in carcinogenesis. Experimental Design: Electromobility gel shift assays were used to evaluate NF-κB DNA binding vitro. functional relevance was assessed by both cDNA array analyses proliferation prostate cancer cells with without exposure an inhibitor, parthenolide. Immunohistochemistry staining for p65 subunit determine...
Preclinical studies of primary cancer cells are typically done after tumors removed from patients or animals at ambient atmospheric oxygen (O
NF-Y is a heterotrimeric transcription factor that specifically recognizes CCAAT box motif found in variety of eukaryotic promoter and enhancer elements. The subunit association DNA binding properties the complex were examined as function redox state using recombinant NF-YA, NF-YB, NF-YC subunits. Reduction NF-YB by dithiothreitol (DTT) was essential for reconstitution specific activity vitro. Approximately 30% Escherichia coli-derived existed intermolecular disulfide-linked dimers. mutants...
Estrogen regulates several biological processes through estrogen receptor alpha (ERalpha) and ERbeta. ERalpha-estrogen signaling is additionally controlled by extracellular signal activated kinases such as AKT. In this study, we analyzed the effect of AKT on genome-wide ERalpha binding in MCF-7 breast cancer cells. Parental AKT-overexpressing cells displayed 4,349 4,359 sites, respectively, with approximately 60% overlap. both cell types, 40% estrogen-regulated genes associate sites; a...
Abstract Recently developed genomics-based tools are allowing repositioning of Food and Drug Administration (FDA)-approved drugs as cancer treatments, which were employed to identify that target stem cells (CSCs) breast cancer. Gene expression datasets CSCs from six studies subjected connectivity map may ameliorate gene patterns unique CSCs. All-trans retinoic acid (ATRA) was negatively connected with in ATRA reduced mammosphere-forming ability a subset cells, correlated induction apoptosis,...
Abstract Circulating microRNAs (miRNA) are emerging as important biomarkers of various diseases, including cancer. Intriguingly, circulating levels several miRNAs lower in patients with cancer compared healthy individuals. In this study, we tested the hypothesis that a miRNA might serve surrogate effects on expression or release distant organs. Here report muscle-enriched miR486 is breast individuals and difference replicated faithfully MMTV-PyMT MMTV-Her2 transgenic mouse models...
Abstract The transcription factor nuclear factor-kappaB (NF- κ B) is constitutively active in several cancers and a target of therapeutic development. We recently developed dimethylaminoparthenolide (DMAPT), clinical grade water-soluble analog parthenolide, as potent inhibitor NF- B demonstrated vitro vivo anti-tumor activities multiple cancers. In this study, we show DMAPT an epigenetic modulator functioning B-dependent -independent manner. DMAPT-mediated inhibition resulted elevated...
// Riesa M. Burnett 1 , Kelly E. Craven 2 Purna Krishnamurthy Chirayu P. Goswami 4 Sunil Badve 3 Peter Crooks 5 William Mathews 6 Poornima Bhat-Nakshatri and Harikrishna Nakshatri 1,2,4 Department of Surgery, Indiana University School Medicine, Indianapolis, IN, USA Biochemistry Molecular Biology, Pathology Laboratory Center for Computational Biology Bioinformatics, Arkansas, Little Rock, AR, Leuchemix, Inc., Woodside, CA, Correspondence to: Nakshatri, email: Keywords : breast cancer, brain...
Abstract Recent reports of widespread genetic variation affecting regulation gene expression raise the possibility significant inter-individual differences in stem-progenitor-mature cell hierarchy adult organs. This has not been explored because paucity methods to quantitatively assess subpopulation normal epithelial cells on individual basis. We report remarkable differentiation capabilities as documented by phenotypic heterogeneity breast. Ethnicity and predisposition are partly...