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Book Characterization of Human Mammary Epithelial Stem Cells

Download or read book Characterization of Human Mammary Epithelial Stem Cells written by and published by . This book was released on 2007 with total page 33 pages. Available in PDF, EPUB and Kindle. Book excerpt: The mammary epithelium in normal adult female mice contains undifferentiated stem cells with extensive in vivo regenerative and self-renewal potential. Analogous cells presumably exist in the mammary glands of adult women, and may be the target cells for transforming mutations that lead to the evolution of breast cancer stem cells. The objective of this grant is to develop a robust, reproducible and specific assay for normal human mammary stem cells, based on a recently-developed xenotransplant methodology. The assay will be applied to identify stem cell markers, develop a methodology to purify stem cells from normal adult breast tissue, and derive information about their frequency and regulation. Considerable progress has been made in developing a stem cell assay in the first year of this grant. We have established conditions that allow human mammary tissue to be regenerated in subrenal xenografts in highly immunodeficient mice, starting with small innocula of dissociated human mammary cells. Furthermore, we have shown that measuring the number of progenitors present in xenografts after several weeks serves as a sensitive and objective "readout" for the presence of primitive stem-like cells among the transplanted cells, allowing this system to be used as a quantitative stem cell assay. Transplants of FACS-separated sub-populations show that these stem cells have a CD49f(high) EpCAM-/low CD31-CD45- phenotype. These findings set the stage for further biological and molecular characterization studies of normal human mammary stem cells and their relationship to human breast cancer stem cells.

Book Detection and Characterization of Human Mammary Stem Cells

Download or read book Detection and Characterization of Human Mammary Stem Cells written by Peter Eirew and published by . This book was released on 2011 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:

Book Regulating Human Mammary Epithelial Stem Cells Transformation

Download or read book Regulating Human Mammary Epithelial Stem Cells Transformation written by Flora Clément and published by . This book was released on 2017 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: It has been shown for a number of cancers that a cell population characterized by stem cell (SC) properties and therapeutic resistance is likely responsible for relapse several years after treatment. Current therapies kill most of the tumor cells, but fail to eradicate the so-called cancer stem cells (CSC). Therefore a complete cure of the disease will require the eradication of the tumor-sustaining CSC. We propose to study these CSC in the context of breast cancer as the existence of CSC as already been highlighted in this epithelia.CD10 is a membrane enzyme able to cleave several peptide of the microenvironment (such as oxytocin, bombesin, enkephalin.. ) that can also interact with intracellular signalling pathway through its direct interaction with PTEN. Our results, and those of the literature, indicate that CD10 enzyme controls the fate of SC and is deregulated in normal breast and cancerous tissues. We showed that CD10 membrane expression allows the maintenance of immature cells partly through its enzymatic function that inhibits mammary stem cells differentiation. As CD10 has been described in breast cancer initiation, progression and resistance, we then decided to test the role of CD10 in tumor context. Our strategy consists in flow cytometry cell sorting for CD10+/CD10- cells to compare the functional properties of both sub-population. Only CD10+ cells are able to regenerate both CD10+ and CD10- subpopulations, and CD10+ cells exhibit higher expression of immature genes. Interestingly, modulating CD10 using stable expression of CD10 in our models and Sh strategies do not mimick the normal functions of CD10, indicating that CD10 could be more a marker of a certain population with immature properties prone to transformation rather than a driver. To better characterize the role of CD10 in luminal breast transformation, we developed a new human mammary model, initiated from immature cells to obtain transformed luminal epithelial cells and their resistant counterpart. We observed a higher level of CD10 expression during mammary epithelial cell transformation process. We then performed a microarray on CD10+ and CD10- subpopulations. Preliminary analysis seems to confirm that CD10 is a potential marker for a stem cell population prone to transformation rather than a direct driver of the cell transformation.

Book Characterization of Breast Cancer Stem Cells

Download or read book Characterization of Breast Cancer Stem Cells written by and published by . This book was released on 2004 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cellular markers which identify putative breast epithelial stem cells have been report Attention has focused on the possibility that certain clinical aspects of breast cancer could result from transformed stem cells residing in the malignant tumor. Breast cancer may therefore originate from neoplastic transformation of normal breast epithelial stem cells. These transformed stem cells may exist in the tumor as rare cells with properties which drive multiple aspects of tumorigenesis. The predictions of this model included slower cell cycle progression greater resistance to DNA damage, increased in vitro invasion, and in vivo tumorigenesis. The application tested the hypothesis that transformed stem cells drive multiple aspects of breast tumorigenesis by functionally characterizing their biological properties. The hypothesis was tested by sorting of putative breast cancer stem cell populations followed by cell cycle analysis, in vitro and in vivo proliferation. and invasion assays, and sensitivity to chemotherapy and radiation induced DNA damage. Putative cancer stem cells generally exhibited slower cell cycle progression, greater resistance to DNA damage, and increased tumor formation. However, the degree of stem-like properties of these cells varied widely depending on the line from which they were isolated.

Book Mammary Stem Cells

    Book Details:
  • Author : Maria dM. Vivanco
  • Publisher : Humana
  • Release : 2022-02-18
  • ISBN : 9781071621929
  • Pages : 354 pages

Download or read book Mammary Stem Cells written by Maria dM. Vivanco and published by Humana. This book was released on 2022-02-18 with total page 354 pages. Available in PDF, EPUB and Kindle. Book excerpt: This second edition provides an overview of recent developments and approaches used by researchers to investigate the properties and functions of mammary epithelial and stem cells, which will contribute to understand the heterogeneity of the mammary gland and of breast cancer. Chapters detail processes used to characterize stem cells, single cell RNA sequencing, computational methods, sophisticated imaging techniques, and a variety of model systems, among others. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Mammary Stem Cells: Methods and Protocols, Second Edition aims to make available protocols used to navigate the intricate behavior of mammary stem cells and to gain further knowledge to take us closer to the design of innovative strategies to prevent and treat breast cancer.

Book Construction and Characterization of Human Mammary Epithelial Cell Lines Containing Mutations in the P53 Or BRCAl Genes

Download or read book Construction and Characterization of Human Mammary Epithelial Cell Lines Containing Mutations in the P53 Or BRCAl Genes written by Raymond White and published by . This book was released on 1997 with total page 18 pages. Available in PDF, EPUB and Kindle. Book excerpt: The overall goal of this project is to identify and characterize the consequences of human mammary epithelial cells (HMEC) that become deficient in normal p53 and BRCA1 gene functions. Our work during the third year of the funding period has produced good progress establishing new systems to create and characterize HMEC with an altered tumor suppressor gene activity. In collaboration with Dr. Bissell's laboratory (UC Berkeley), we have established three-dimensional culture system in our laboratory. This system will allow us to see differences of the growth properties, expression and distribution of certain cell lineage markers, morphology and behavior in between normal cells and partially transformed cells. Our recent acquisition of a Microarray Spotting and Scanning instrument enabled us the use of this robust and sensitive microarray technology to establish genetic expression profiles from any cell source of interest. We have also applied the differential display protocol to identify genes with altered expression in a model system of normal and neoplastic epithelial cells. We firmly believe that these new systems will provide us critical information to our understanding of breast carcinogenesis.

Book Construction and Characterization of Human Mammary Epithelial Cell Lines Containing Mutations in the P53 Or BRCA1 Genes

Download or read book Construction and Characterization of Human Mammary Epithelial Cell Lines Containing Mutations in the P53 Or BRCA1 Genes written by and published by . This book was released on 1999 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: The overall goal of this project is to identify and characterize the consequences of human mammary epithelial cells (HMEC) that become deficient in normal p53 or BRCA-l gene functions. We have created retroviral vectors which allow us conditionally express the E6/E7 gene of human papillomavirus type 16 (HPVl6), dominant-negative p53 gene, or anti-sense BRCA-l gene. The consequences of transduction of these viral constructs into primary human mammary epithelial cells will be discovered through controlled in vitro comparisons between genetically altered derivatives and their isogenic parent cells. As we proposed in our last report, we are now focused our efforts on microarray-based comparisons to identify breast cancer related genes. During the past year we have successfully implemented the Microarray Spotting and Scanning techniques. This includes development of robust fluorescent labeling and hybridization protocols as well as the preparation and testing of over 23,000 minimally redundant cDNA target samples for deposition on the microarray slides. We have compared expression profiles from several distinct breast cell lines we had created. We believe that this system will provide us critical information to our understanding of early breast carcinogenesis.

Book Characterization of Breast Cancer Stem Cells  Addendum

Download or read book Characterization of Breast Cancer Stem Cells Addendum written by and published by . This book was released on 2005 with total page 14 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cellular markers which identify putative breast epithelial stem cells have been reported. Certain clinical aspects of breast cancer could result from transformed stem cells in the malignant tumor. Breast cancer may therefore originate from neoplastic transformation of normal breast epithelial stem cells. These transformed stem cells exist in the tumor as rare cells with properties that drive aspects of tumorigenesis. This model predicts slower cell cycle progression, greater resistance to DNA damage, increased in vitro invasion, and in vivo tumorigenesis. We tested the hypothesis that transformed stem cells drive multiple aspects of breast tumorigenesis by functionally characterizing their biological properties. The hypothesis was tested by sorting of putative breast cancer stem cell populations followed by cell cycle analysis, in vitro and in vivo proliferation and invasion assays, and sensitivity to chemotherapy and radiation induced DNA damage. Putative cancer stem cells generally exhibited slower cell cycle progression, greater resistance to DNA damage, and increased tumor formation. However, the stem-like properties of these cells varied widely depending on the line from which they were isolated.

Book Characterization of an In Vitro Human Breast Epithelial Organoid System

Download or read book Characterization of an In Vitro Human Breast Epithelial Organoid System written by and published by . This book was released on 1999 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: The objectives of this study are: (1) to identify factors that regulate the growth and differentiation of organoids formed by two types of normal human breast epithelial cells (HBEC) in Matrigel; (2) to characterize the expression and function of estrogen receptors (ER) in normal and in vitro neoplastically transformed HBEC; and (3) to determine if a HBEC type with stem cell characteristics (Type I) is more susceptible to telomerase activation and immortalization. The major results are: (1) Type I HBEC in conjunction with Type II cells are capable of forming ductal and end bud or lobule 1-like structures in Matrigel which preserve the undifferentiated state of HBEC for a long time, evidence that Type I HBEC are stem cells; (2) Type I normal HBEC and their neoplastically transformed clones express a variant ER-A in vitro on plastic while expressing a wild type ER-A in tumors developed in nude mice or grown in vitro in Matrigel (3) The -46kd variant ER-A is the result of splicing deletion of exon 1 in ER-A transcript; Type I HBEC use promoter A while immortal and tumorigenic Type I cells use both promoter A and C for transcription; and (4) high susceptibility of Type I HBEC to telomerase activation and immortalization, a basis on which Type I EBEC (stem cells) are major targets for carcinogenesis.

Book Construction and Characterization of Human Mammary Epithelial Cell Lines Containing Mutations in P53 Or BRCA1 Genes

Download or read book Construction and Characterization of Human Mammary Epithelial Cell Lines Containing Mutations in P53 Or BRCA1 Genes written by and published by . This book was released on 1995 with total page 12 pages. Available in PDF, EPUB and Kindle. Book excerpt: To study the effects of inactivating mutations in the p53 and BRCA1 genes early in the breast cancer pathway, we will develop genetically defined human mammary epithelial cell (HMEC) lines by introducing heterozygous and homozygous mutations of each gene using homologous recombination. Additionally, we will construct HMEC lines deficient in p53 protein by expressing the E6 gene of human papillomavirus type 16 (HPV16), which increases the rate of degradation of the p53 protein. The consequences of these genetic changes for cell metabolism will be discovered through controlled in vitro comparisons between genetically altered derivatives and their isogenic parent cells. One level of comparison will involve observations of their growth properties, expression of certain cell lineage markers (e.g. keratins, integrins), morphology and behavior. At another level, we will take a global approach to the discovery of metabolic changes associated with genetic alterations in early tumorigenesis by constructing substraction cDNA libraries and by differential display to reveal changes in mRNA transcription that are associated with loss of activity of each of these genes. Clones showing differential expression will be sequenced in our Sequence Core Facility at the University of Utah to reveal genes potentially critical in growth control, by reference to databanks.

Book

    Book Details:
  • Author :
  • Publisher :
  • Release : 1965
  • ISBN : 9780670064663
  • Pages : 50 pages

Download or read book written by and published by . This book was released on 1965 with total page 50 pages. Available in PDF, EPUB and Kindle. Book excerpt: Raised to be a thief, blind orphan Peter Nimble, age ten, steals from a mysterious stranger three pairs of magical eyes, that lead him to a hidden island where he must decide to become a hero or resume his life of crime.

Book The Role of Mammary Epithelial Stem Cells in the Transition from Normal to Malignant Epithelium

Download or read book The Role of Mammary Epithelial Stem Cells in the Transition from Normal to Malignant Epithelium written by and published by . This book was released on 2001 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: A steadily growing body of evidence indicates that mouse and human mammary cancers present as clonal diseases that depend upon genetic alterations both for their initiation and progression. It is considered likely, but not proven, that the only cells of any tissue able to pass on genetic aberrations to their progeny are those that retain the capacity for cell division and that do not become terminally differentiated. This hypothesis has renewed interest in the biology and characteristics of stem cells in many tissues, with the notion that such information will be useful for the prevention, detection and therapy of the disease. In recent years it has been shown that even tissues like brain, heart, and skeletal muscle, that were previously thought to have no stem cell compartment do, in fact, have a population of stem cells. Research on the nature and characteristics of hematopoietic stem cells has produced stem cell markers and a large body of information on mechanisms of oncogenesis in myelocytes and lymphocytes. These advances have made it apparent that we need a thorough knowledge of normal growth and development and thus of the stem cell population of the mammary epithelium to understand and treat breast cancer. If the stem cell compartment plays an important role in the transition of mammary epithelium from a normal to a malignant cell population, determining the dynamics, regulation, and biology of these cells could be of considerable value to the prevention and therapy of cancer.