Open Access. Powered by Scholars. Published by Universities.®

Biochemistry, Biophysics, and Structural Biology Commons

Open Access. Powered by Scholars. Published by Universities.®

Molecular Biology

Breast cancer

Institution
Publication Year
Publication
Publication Type
File Type

Articles 1 - 30 of 35

Full-Text Articles in Biochemistry, Biophysics, and Structural Biology

Signaling Pathways Induced By Leptin During Epithelial(-)Mesenchymal Transition In Breast Cancer, Monserrat Olea-Flores, Juan Carlos Juarez-Cruz, Miguel A. Mendoza-Catalan, Teresita Padilla-Benavides, Napoleon Navarro-Tito Nov 2018

Signaling Pathways Induced By Leptin During Epithelial(-)Mesenchymal Transition In Breast Cancer, Monserrat Olea-Flores, Juan Carlos Juarez-Cruz, Miguel A. Mendoza-Catalan, Teresita Padilla-Benavides, Napoleon Navarro-Tito

Open Access Articles

Leptin is an adipokine that is overexpressed in obese and overweight people. Interestingly, women with breast cancer present high levels of leptin and of its receptor ObR. Leptin plays an important role in breast cancer progression due to the biological processes it participates in, such as epithelial(-)mesenchymal transition (EMT). EMT consists of a series of orchestrated events in which cell(-)cell and cell(-)extracellular matrix interactions are altered and lead to the release of epithelial cells from the surrounding tissue. The cytoskeleton is also re-arranged, allowing the three-dimensional movement of epithelial cells into the extracellular matrix. This transition provides ...


Deciphering The Role Of Human Arylamine N-Acetyltransferase 1 (Nat1) In Breast Cancer Cell Metabolism Using A Systems Biology Approach., Samantha Marie Carlisle Aug 2018

Deciphering The Role Of Human Arylamine N-Acetyltransferase 1 (Nat1) In Breast Cancer Cell Metabolism Using A Systems Biology Approach., Samantha Marie Carlisle

Electronic Theses and Dissertations

Background: Human arylamine N-acetyltransferase 1 (NAT1) is a phase II xenobiotic metabolizing enzyme found in almost all tissues. NAT1 can additionally hydrolyze acetyl-coenzyme A (acetyl-CoA) in the absence of an arylamine substrate. NAT1 expression varies inter-individually and is elevated in several cancers including estrogen receptor positive (ER+) breast cancers. Additionally, multiple studies have shown the knockdown of NAT1, by both small molecule inhibition and siRNA methods, in breast cancer cells leads to decreased invasive ability and proliferation and decreased anchorage-independent colony formation. However, the exact mechanism by which NAT1 expression affects cancer risk and progression remains unclear. Additionally, consequences ...


Etv4 Transcription Factor And Mmp13 Metalloprotease Are Interplaying Actors Of Breast Tumorigenesis, Mandy Dumortier, Franck Ladam, Isabelle Damour, Sophie Vacher, Ivan Bieche, Nathalie Marchand, Yvan De Launoit, David Tulasne, Anne Chotteau-Lelievre Jul 2018

Etv4 Transcription Factor And Mmp13 Metalloprotease Are Interplaying Actors Of Breast Tumorigenesis, Mandy Dumortier, Franck Ladam, Isabelle Damour, Sophie Vacher, Ivan Bieche, Nathalie Marchand, Yvan De Launoit, David Tulasne, Anne Chotteau-Lelievre

Open Access Articles

BACKGROUND: The ETS transcription factor ETV4 is involved in the main steps of organogenesis and is also a significant mediator of tumorigenesis and metastasis, such as in breast cancer. Indeed, ETV4 is overexpressed in breast tumors and is associated with distant metastasis and poor prognosis. However, the cellular and molecular events regulated by this factor are still misunderstood. In mammary epithelial cells, ETV4 controls the expression of many genes, MMP13 among them. The aim of this study was to understand the function of MMP13 during ETV4-driven tumorigenesis.

METHODS: Different constructs of the MMP13 gene promoter were used to study the ...


Identification Of A Novel Invasion-Promoting Region In Insulin Receptor Substrate 2, Jose Mercado-Matos, Jenny Janusis, Sha Zhu, Samuel S. Chen, Leslie M. Shaw Jun 2018

Identification Of A Novel Invasion-Promoting Region In Insulin Receptor Substrate 2, Jose Mercado-Matos, Jenny Janusis, Sha Zhu, Samuel S. Chen, Leslie M. Shaw

University of Massachusetts Medical School Faculty Publications

Although the insulin receptor substrate (IRS) proteins IRS1 and IRS2 share considerable homology and activate common signaling pathways, their contributions to breast cancer are distinct. IRS1 has been implicated in the proliferation and survival of breast tumor cells. In contrast, IRS2 facilitates glycolysis, invasion, and metastasis. To determine the mechanistic basis for IRS2-dependent functions, we investigated unique structural features of IRS2 that are required for invasion. Our studies revealed that the ability of IRS2 to promote invasion is dependent upon upstream insulin-like growth factor 1 receptor (IGF-1R)/insulin receptor (IR) activation and the recruitment and activation of phosphatidylinositol 3-kinase (PI3K ...


Deciphering The Roles Of Δnp63 In Regulating Epithelial To Mesenchymal Transition, Cancer Progression And Metastasis, Ngoc Bui May 2018

Deciphering The Roles Of Δnp63 In Regulating Epithelial To Mesenchymal Transition, Cancer Progression And Metastasis, Ngoc Bui

UT GSBS Dissertations and Theses (Open Access)

p63 is a member of the p53 family, a well-known tumor suppressor which is considered the guardian of the genome. The TP63 gene encodes multiple isoforms that can be categorized into two main isoforms, TAp63 and ΔNp63, which are expressed in different cellular compartments and have distinct functions in many biological processes. While the Flores laboratory identified TAp63 as a tumor and metastasis suppressor, the precise roles of ΔNp63 isoforms in tumorigenesis and metastasis remain elusive. ΔNp63 is the predominant p63 isoform expressed in the epidermis and plays essential roles in regulating epidermal development and homeostasis. Utilizing a ΔNp63-conditional ...


The Effect Of Target-Specific Biomolecules In Breast Cancer, Mohannad Garoub Jun 2017

The Effect Of Target-Specific Biomolecules In Breast Cancer, Mohannad Garoub

FIU Electronic Theses and Dissertations

Cancer is the second leading cause of mortality in the United States and the World, therefore, early effective prevention, diagnosis, and therapy is needed. Estrogens play a major role in the initiation and progression of breast cancer. Elevated lifetime exposure to estrogens is associated with an increased risk of developing breast cancer. Estrogens through influencing mitochondria contribute to estrogen induced breast carcinogenesis; however, the exact mitochondrial mechanisms underlying the estrogen carcinogenic effect in breast tissue are not clearly understood. For this dissertation, the mitotoxic and cytotoxic effects of triphenylphosphonium cation (TPP) and Origanum majorana organic extract (OME) as well as ...


Differential Involvement Of The Microtubule Cytoskeleton In Insulin Receptor Substrate 1 (Irs-1) And Irs-2 Signaling To Akt Determines The Response To Microtubule Disruption In Breast Carcinoma Cells, Jose Mercado-Matos, Jennifer L. Clark, Andrew J. Piper, Jenny Janusis, Leslie M. Shaw May 2017

Differential Involvement Of The Microtubule Cytoskeleton In Insulin Receptor Substrate 1 (Irs-1) And Irs-2 Signaling To Akt Determines The Response To Microtubule Disruption In Breast Carcinoma Cells, Jose Mercado-Matos, Jennifer L. Clark, Andrew J. Piper, Jenny Janusis, Leslie M. Shaw

UMass Metabolic Network Publications

The insulin receptor substrate (IRS) proteins serve as essential signaling intermediates for the activation of PI3K by both the insulin-like growth factor 1 receptor (IGF-1R) and its close family member, the insulin receptor (IR). Although IRS-1 and IRS-2 share significant homology, they regulate distinct cellular responses downstream of these receptors and play divergent roles in breast cancer. To investigate the mechanism by which signaling through IRS-1 and IRS-2 results in differential outcomes, we assessed the involvement of the microtubule cytoskeleton in IRS-dependent signaling. Treatment with drugs that either stabilize or disrupt microtubules reveal that an intact microtubule cytoskeleton contributes to ...


Rna-Sequencing Reveals Direct Targets Of Tumor Suppressor Mir-203 In Human Mammary Epithelial Cells, Alexander P. Boardman, Victoria E. Pedanou, Tessa M. Simone, Michael R. Green May 2017

Rna-Sequencing Reveals Direct Targets Of Tumor Suppressor Mir-203 In Human Mammary Epithelial Cells, Alexander P. Boardman, Victoria E. Pedanou, Tessa M. Simone, Michael R. Green

Senior Scholars Program

Background: Breast cancer is the leading cause of cancer-related mortality in women worldwide. Since a significant portion of cases present with or progress to metastatic disease, furthering our understanding of metastasis is critical to develop better treatments. Epithelial cells maintain contact with the extracellular matrix (ECM) predominantly via integrin engagement, a process required for tissue integrity and barrier function. In non-transformed cells, loss of ECM adhesion promotes a specialized form of programmed cell death, anoikis. In order for efficient metastasis to occur, breast tumor cells must evade anoikis. miR-203, known to be down-regulated in several cancers, was found by our ...


Runx1 And Breast Cancer, Jose Mercado-Matos, Asia N. Matthew-Onabanjo, Leslie M. Shaw Apr 2017

Runx1 And Breast Cancer, Jose Mercado-Matos, Asia N. Matthew-Onabanjo, Leslie M. Shaw

UMass Metabolic Network Publications

News on: Runx1 stabilizes the mammary epithelial cell phenotype and prevents epithelial to mesenchymal transition, by Hong et al. Oncotarget. 2017; 8:17610-27. doi: 10.18632/oncotarget.15381.


Mammalian Swi/Snf Enzymes And The Epigenetics Of Tumor Cell Metabolic Reprogramming, Jeffrey A. Nickerson, Qiong Wu, Anthony N. Imbalzano Apr 2017

Mammalian Swi/Snf Enzymes And The Epigenetics Of Tumor Cell Metabolic Reprogramming, Jeffrey A. Nickerson, Qiong Wu, Anthony N. Imbalzano

UMass Metabolic Network Publications

Tumor cells reprogram their metabolism to survive and grow in a challenging microenvironment. Some of this reprogramming is performed by epigenetic mechanisms. Epigenetics is in turn affected by metabolism; chromatin modifying enzymes are dependent on substrates that are also key metabolic intermediates. We have shown that the chromatin remodeling enzyme Brahma-related gene 1 (BRG1), an epigenetic regulator, is necessary for rapid breast cancer cell proliferation. The mechanism for this requirement is the BRG1-dependent transcription of key lipogenic enzymes and regulators. Reduction in lipid synthesis lowers proliferation rates, which can be restored by palmitate supplementation. This work has established BRG1 as ...


Clinicopathology And Molecular Determinants Underlying Benign Breast And Breast Cancer Lesions, Andreana Holowatyj Holowatyj Jan 2017

Clinicopathology And Molecular Determinants Underlying Benign Breast And Breast Cancer Lesions, Andreana Holowatyj Holowatyj

Wayne State University Dissertations

Despite converging incidence rates for breast cancers by race, disparities in mortality persist where black women suffer from poorer prognosis compared to white counterparts. To understand the clinical, demographic, and molecular characteristics underlying these disparities, we examined differences among patients with breast cancer to understand the role of human epidermal growth factor receptor 2 (HER2) status, age, and race/ethnicity among women diagnosed with hormone receptor-positive breast cancer, and disparities in surgical therapy among female patients with early stage young-onset breast cancer. Benign breast disease, another known risk factor for breast cancer, includes a histological spectrum of lesions, could contribute ...


The Rodent Parvovirus H-1 And Its Potential In Combination With Tien Hsien Liquid As A Treatment For Breast Cancer, Hayley I. Spires Nov 2016

The Rodent Parvovirus H-1 And Its Potential In Combination With Tien Hsien Liquid As A Treatment For Breast Cancer, Hayley I. Spires

Selected Honors Theses

Breast cancer is responsible for 12% of cancer diagnoses each year, and it is the leading cause of cancer-related mortality in women worldwide. Current treatments have provided some success in combatting the disease but are not considered a final solution. The framework for how researchers approach cancer has continued to change, and this includes the introduction of oncolytic viruses as novel therapeutics for cancer. The rodent parvovirus H-1 has shown strong potential in clinical and subclinical trials, but its S phase dependency limits its usefulness against cancer stem cell populations. Tien Hsien Liquid is commerically available, nontoxic, and has shown ...


Investigating The Roles Of Δnp63 As A Suppressor Of Migration, Invasion, And Metastasis, Ramon E. Flores Gonzalez Aug 2016

Investigating The Roles Of Δnp63 As A Suppressor Of Migration, Invasion, And Metastasis, Ramon E. Flores Gonzalez

UT GSBS Dissertations and Theses (Open Access)

Cancer is one of the leading causes of death and disease in the world. Considerable resources are spent to study and understand cancer, with the hope of developing new treatments and eventually cures that will help millions of people. Efforts to understand cancer are hindered by its inherent complexity and instability. Nonetheless, understanding the basics of tumor development and progression are the key to focused on studying the role of ΔNp63 in cancer, a p53 family member known to be involved in epithelial development, microRNA biogenesis, and stem cell maintenance. Using the strength of in vivo mouse models, we found ...


Tamoxifen Mediated Metabolic Stress: Molecular Mechanism And Therapeutic Opportunities, Natalie Ann Daurio Jan 2016

Tamoxifen Mediated Metabolic Stress: Molecular Mechanism And Therapeutic Opportunities, Natalie Ann Daurio

Publicly Accessible Penn Dissertations

Tamoxifen is the most widely used adjuvant chemotherapeutic for the treatment of estrogen receptor (ER) positive breast cancer, yet a large body of clinical and preclinical data indicates that tamoxifen can modulate multiple cellular processes independently of ER status. Here, we describe the ER-independent effects of tamoxifen on tumor metabolism. Using combined pharmacological and genetic knockout approaches, we demonstrate that tamoxifen inhibits oxygen consumption via inhibition of mitochondrial complex I, resulting in an increase in the AMP/ATP ratio and activation of the AMPK signaling pathway in vitro and in vivo. We also show that tamoxifen-induced cytotoxicity is modulated by ...


Prophylactic Cranial Irradiation Reduces The Incidence Of Brain Metastasis In A Mouse Model Of Metastatic Breast Cancer, Daniel L. Smith Aug 2015

Prophylactic Cranial Irradiation Reduces The Incidence Of Brain Metastasis In A Mouse Model Of Metastatic Breast Cancer, Daniel L. Smith

UT GSBS Dissertations and Theses (Open Access)

Prophylactic cranial irradiation (PCI) is a preventative whole-brain irradiation technique used to reduce the incidence of brain metastasis and improve overall survival in select patients with small cell lung cancer and acute lymphoblastic leukemia. A population of breast cancer patients – stage IV, HER2+ or triple-negative – has emerged as having a high risk of developing brain metastases. Because only 10-20% of breast cancer patients diagnosed with brain metastases survive longer than one year, in this high-risk population the benefit of PCI – potential for reduced incidence of brain metastasis and improved overall survival – may outweigh the risks – radiation toxicity. The objective of ...


The Cancer Genome Atlas (Tcga): Breast And Ovarian Cancers, Laura Ann Riccio May 2015

The Cancer Genome Atlas (Tcga): Breast And Ovarian Cancers, Laura Ann Riccio

Senior Honors Projects

The field of genomics originated in the 1970’s starting with the sequencing of small organisms’ genomes such as the bacterium, Haemophilus influenzae, and the yeast, Saccharomyces cerevisiae. A genome is the complete ordered sequence of DNA bases (A, C, G, and T) comprising all of the protein- and RNA-coding genes, as well as all of the regulatory sequences necessary for the construction of an organism. Over time, scientists sequenced the genomes of larger and more complex organisms, eventually leading to the sequencing of the human genome. The Human Genome Project (HGP) was initiated in 1990 and took over ten ...


Stat6 Mediates Interleukin-4 Growth Inhibition In Human Breast Cancer Cells, Jennifer L. Gooch, B. Christy, D. Yee Mar 2015

Stat6 Mediates Interleukin-4 Growth Inhibition In Human Breast Cancer Cells, Jennifer L. Gooch, B. Christy, D. Yee

Jennifer L. Gooch

In addition to acting as a hematopoietic growth factor, interleukin-4 (IL-4) inhibits growth of some transformed cells in vitro and in vivo. In this study, we show that insulin receptor substrate (IRS)-1, IRS-2, and signal transducer and activator of transcription 6 (STAT6) are phosphorylated following IL-4 treatment in MCF-7 breast cancer cells. STAT6 DNA binding is enhanced by IL-4 treatment. STAT6 activation occurs even after IRS-1 depletion, suggesting the two pathways are independent. To examine the role of STAT6 in IL-4-mediated growth inhibition and apoptosis, a full-length STAT6 cDNA was transfected into MCF-7 cells. Transient overexpression of STAT6 resulted ...


Proteasome Inhibition As A Potential Anti-Breast Cancer Therapy: Mechanisms Of Action And Resistance-Reversing Strategies, Rahul Rajesinh Deshmukh Jan 2015

Proteasome Inhibition As A Potential Anti-Breast Cancer Therapy: Mechanisms Of Action And Resistance-Reversing Strategies, Rahul Rajesinh Deshmukh

Wayne State University Dissertations

AMPK activation and Ubiquitin Proteasome System (UPS) inhibition have gained great attention as therapeutic strategies for the treatment of certain types of cancers. While AMPK serves as a master regulator of cellular metabolism, UPS regulates protein homeostasis. Although the crosstalk between them is suggested, the relationship between these two important pathways is not very clear. We observed that proteasome inhibition leads to AMPK activation in human breast cancer cells. We report that a variety of proteasome inhibitors activate AMPK in all of the tested cancer cell lines. Our data using Liver Kinase B1 (LKB1)-deficient cancer cells suggests that proteasome ...


Jab1 Negatively Regulates Pten And Promotes Resistance To Trastuzumab In Her2-Positive Breast Cancer, Thuy T. Vu Dec 2014

Jab1 Negatively Regulates Pten And Promotes Resistance To Trastuzumab In Her2-Positive Breast Cancer, Thuy T. Vu

UT GSBS Dissertations and Theses (Open Access)

HER2-positive breast cancer, which is characterized by the over-expression of the HER2 onco-protein, accounts for approximately 20% of all breast cancer cases. Trastuzumab (Herceptin), the first targeted therapy approved for HER2-positive disease, potently prevents the activation of signaling pathways downstream of HER2 and significantly improves patients’ outcomes. However, resistance to trastuzumab is inevitable; such resistance can occur through reduced expression of PTEN protein.

Jab1 is over-expressed in 50% of primary cancers and 90% of metastatic tumors. Our lab previously showed that depletion of Jab1 in combination with trastuzumab treatment up-regulated PTEN in mouse xenografts refractory to trastuzumab. PTEN was not ...


1,25-Dihydroxyvitamin D Alters Lipid Metabolism And Epithelialto- Mesenchymal Transition In Metastatic Epithelial Breast Cancer Cells, Alle Nicole Barnard Jul 2014

1,25-Dihydroxyvitamin D Alters Lipid Metabolism And Epithelialto- Mesenchymal Transition In Metastatic Epithelial Breast Cancer Cells, Alle Nicole Barnard

Open Access Theses

Evidence suggests that high vitamin D status (marked by serum 25-hydroxyvitamin D, 25(OH)2 D) is associated with a decreased risk of breast cancer. It has been established that 1,25-dihydroxyvitamin D (1,25(OH) 2 D) can alter glycolysis and the Krebs cycle of breast cancer cells (Jiang et al., 2010; Zheng et al., 2013) but little information is available on 1,25(OH) 2 D's alterations of lipid metabolism in breast cancer cells. Thus, the current research investigates if there was an effect of 1,25(OH) 2 D on proteins that regulate lipid metabolism in ...


The Regulation Of Microrna Biogenesis By Ribosome-Interacting Proteins, Brian Pickering May 2014

The Regulation Of Microrna Biogenesis By Ribosome-Interacting Proteins, Brian Pickering

UT GSBS Dissertations and Theses (Open Access)

MicroRNA (miRNA) are small, non-coding RNAs that affect gene expression through degradation of complementary mRNA targets or inhibition of translation. As they affect approximately 50% of all cellular processes, miRNA are tightly regulated by the cell through transcriptional and post-transcriptional mechanisms. Transcribed miRNA are capped and polyadenylated (referred to as pri-miRNA) which are cleaved by Drosha and DGCR8 to generate 60-90 nucleotide precursor miRNA. The precursors are cleaved again by Dicer and loaded into the RNA-induced silencing complex (RISC) of which Argonaute 2 is the functional component. Many of the proteins involved in miRNA biogenesis share a common role in ...


Neurotrophins And Their Effects On Breast Cancer Cell Proliferation And Migration, Kayla Elise Minser Apr 2014

Neurotrophins And Their Effects On Breast Cancer Cell Proliferation And Migration, Kayla Elise Minser

Open Access Theses

Cancer is a large health issue in all parts of the world. In the United States alone, approximately 1 in 4 deaths are cancer related. Breast cancer is a particularly prevalent form, accounting for a little over 14 percent of all cancer incidence. The largest obstacle to overcome for breast cancer morbidity is metastasis. Over 90 percent of all breast cancer related deaths are due to metastasis. Because metastasis is a complex, multi-step process, it is difficult to treat. A recent observation in the Kirshner lab has revealed a type of phenotypic plasticity, where migratory cancer cells have a neuronal-like ...


Requirements Of Rab5 Activity In Highly Invasive Breast Cancer Cell Lines, Nicole Porther, M Alejandro Barbieri Dec 2013

Requirements Of Rab5 Activity In Highly Invasive Breast Cancer Cell Lines, Nicole Porther, M Alejandro Barbieri

Nicole Porther

Rab5 expression in cancer has been associated with the disease progression and prognosis. We have previously shown that growth factor-directed cell invasion and migration was dependent on Rab5 activation in non-invasive breast cancer cells. However, hardly any data is available regarding the role of Rab5 in invasive cells in the presence of growth factor.  In our present study, we report that the invasive and migratory properties of the highly invasive breast cancer cell line, MDAMB-231, were abrogated in cells expressing the inactive (GDP-bound) form of Rab5 irrespective of growth factor stimulation; while the invasive potential of breast cancer cell lines ...


Proteomic And Biochemical Studies Of Estrogen-Mediated Signaling And Novel Estrogen Receptor-Interacting Proteins In Breast Cancer Cells, Zhenqi Zhou Aug 2013

Proteomic And Biochemical Studies Of Estrogen-Mediated Signaling And Novel Estrogen Receptor-Interacting Proteins In Breast Cancer Cells, Zhenqi Zhou

Theses and Dissertations

Estrogen plays essential roles in the growth, development, and homeostasis of a number of tissues, and can also be linked to the growth of breast cancer. The biological activities of estrogen are mediated by estrogen receptors (ERs) ERá and ERâ, and also orphan G-protein-coupled receptor 30 (GPR30). In order to identify novel proteins that are involved in ER-mediated actions of estrogen, we used mass spectrometry-based quantitative proteomic methods to systematically profile global protein expression in responses to E2 (17â-estradiol) stimulation in human breast cancer cell, and identify and characterize cellular novel proteins that are associated with ERs in breast cancer ...


Interaction Between Brk And Her2 In Breast Cancer, Midan Ai May 2013

Interaction Between Brk And Her2 In Breast Cancer, Midan Ai

UT GSBS Dissertations and Theses (Open Access)

INTERACTION BETWEEN BRK AND HER2 IN BREAST CANCER

Midan Ai, Ph.D.

Supervisory Professor: Zhen Fan, M.D.

Breast tumor kinase (Brk) is a nonreceptor protein-tyrosine kinase that is highly expressed in approximately two thirds of breast cancers but is not detectable or is expressed at very low levels in normal mammary epithelium. Brk plays important roles in promoting proliferation, survival, invasion, and metastasis of breast cancer cells, but the mechanism(s) of which remain largely unknown. Recent studies showed that Brk is frequently co-overexpressed with human epidermal growth factor receptor-2 (HER2) and is physically associated with HER2 in breast ...


Expansion Of Breast Cancer Stem Cells With Fibrous Scaffolds, Sheng Feng, Pang-Kuo Lo, Shou Liu, Xinfeng Liu, Hexin Chen, Qian Wang Jan 2013

Expansion Of Breast Cancer Stem Cells With Fibrous Scaffolds, Sheng Feng, Pang-Kuo Lo, Shou Liu, Xinfeng Liu, Hexin Chen, Qian Wang

Faculty Publications

Cancer stem cells (CSCs) are hypothesized as tumor-initiating cells within tumors and main contributors of tumor growth, metastasis and recurrence. Mammary cancer cells, MCF-7 cells, were cultured on 3D polycaprolactone (PCL) fibrous scaffolds, showing an increased proportion of CSCs. The expression of stem cell markers, including OCT3/4 and SOX2, and breast CSC-specific markers, SOX4 and CD49f, was significantly upregulated, and the mammosphere-forming capability in cells cultured on PCL fibrous scaffolds increased. The fibrous scaffolds also induced the elongation of MCF-7 cells and extended cell proliferation. The increase of CSC properties after being cultured on fibrous scaffolds was further confirmed ...


Acidic Pericellular Ph: Effects On Proteolysis And Gene Expression As Determined In 3d Models Of Breast Carcinoma, Jennifer M. Rothberg Jan 2013

Acidic Pericellular Ph: Effects On Proteolysis And Gene Expression As Determined In 3d Models Of Breast Carcinoma, Jennifer M. Rothberg

Wayne State University Dissertations

Among the non-cellular microenvironmental factors that contribute to malignancy of solid tumors is an acidic peritumoral pH. The first objective was to determine if an acidic extracellular pH observed in vivo (i.e., pHe 6.8) affects the activity of proteases, such as cathepsin B, that contribute to degradation of collagen IV by tumor cells when grown in biologically relevant three-dimensional cultures. At pHe 6.8 there were increases in pericellular active cysteine cathepsins and in degradation of DQ-collagen IV, which was partially blocked by a cathepsin B inhibitor. Imaging probes for active cysteine cathepsins localized to tumors in vivo ...


Identification Of Epithelial Stromal Interaction 1 And Epidermal Growth Factor Receptor As Novel Kruppel-Like Factor 8 Targets In Promoting Breast Cancer Progression, Tianshu Li Jan 2013

Identification Of Epithelial Stromal Interaction 1 And Epidermal Growth Factor Receptor As Novel Kruppel-Like Factor 8 Targets In Promoting Breast Cancer Progression, Tianshu Li

Electronic Theses and Dissertations

Breast cancer is the major cause of cancer death among women worldwide. Understanding the mechanisms underlying breast cancer progression remains urgent for developing effective treatment strategies to eliminate breast cancer mortality. Our recent studies have demonstrated that Krüppel-like transcriptional factor 8 (KLF8) plays a critical role for breast cancer progression. Other studies have shown that Epithelial stromal interaction 1 (EPSTI1), a recently identified stromal fibroblast-induced gene in non-invasive breast cancer cells and epidermal growth factor receptor (EGFR) are highly overexpressed in aggressively invasive breast carcinomas including triple negative breast cancers. In this thesis project, we demonstrate high co-overexpression of KLF8 ...


The Role Of Brca1 Domains And Motifs In Tumor Suppression, Aneliya Velkova Jan 2011

The Role Of Brca1 Domains And Motifs In Tumor Suppression, Aneliya Velkova

Graduate Theses and Dissertations

ABSTRACT

Individuals that carry deleterious mutations in the breast and ovarian cancer susceptibility gene 1 (BRCA1) have much more elevated risk to develop breast and/or ovarian cancer than the individuals from the general population. The BRCA1 gene product has been implicated in several aspects of the DNA damage response, but its biochemical function in these processes has remained elusive. In order to probe BRCA1 functions we conducted a yeast two-hybrid screening to identify interacting partners to a conserved motif (Motif 6) in the central region of BRCA1. In this dissertation, we report the identification of the actin-binding protein Filamin ...


In Vivo Investigations Of Polymer Conjugates As Therapeutics, Elizabeth M. Henchey Jan 2011

In Vivo Investigations Of Polymer Conjugates As Therapeutics, Elizabeth M. Henchey

Masters Theses 1911 - February 2014

Polymer conjugates offer a way to introduce materials into the body that would normally be rejected or cause toxicity. Two polymers are investigated in vivo for uses in chemotherapeutic delivery, protein therapeutics, and DNA transfection. A novel polymer, polyMPC, has the ability to increase doxorubicin loading and its solubility, and is conjugated in a way to release its payload in a low pH environment. Through its conjugation, blood clearance time of doxorubicin is increased, and thus tumor exposure to the drug is increased with a single administration. It can be administered at ten times the concentration of free doxorubicin, and ...