• Libraries
    • Log in to:
    View Item 
    •   MSpace Home
    • Faculty of Graduate Studies (Electronic Theses and Practica)
    • FGS - Electronic Theses and Practica
    • View Item
    •   MSpace Home
    • Faculty of Graduate Studies (Electronic Theses and Practica)
    • FGS - Electronic Theses and Practica
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Upper limb modelling, dynamic analysis, and force distribution using fuzzy logic

    Thumbnail
    View/Open
    NQ51634.pdf (13.66Mb)
    Date
    1999-10-01
    Author
    Coutts, Amanda Susan
    Metadata
    Show full item record
    Abstract
    Breast cancer is a hormonally responsive cancer and hormones, including estrogen, are required for breast cancer growth. The evolution of breast cancer into an estrogen-independent growth phenotype is thought to be an important step in the progression of breast cancer to hormone-independence and endocrine therapy resistance. Understanding the factors that contribute to the development of an estrogen-nonresponsive growth phenotype is of major importance in terms of breast cancer therapeutics. Resistance to endocrine therapies may be due to a number of factors, including loss of estrogen receptor-alpha (ER-_) expression, but most tumours that have developed resistance to endocrine therapy remain ER-_ positive. The mechanisms responsible for the development of estrogen-independence in the presence of continued expression of ER-_ are poorly understood. In order to address this, a breast cancer cell model of apparent estrogen-independence was developed. An estrogen-nonresponsive cell fine, T5-PRF, was developed from T5 (ER-_) positive and estrogen-responsive) human breast cancer cells by chronically depleting the cells of estrogen in long-term culture. The T5-PRF cells are insensitive to the growth-stimulatory effects of estrogen while still retaining expression of the (ER-_) The tissue matrix consists of linkages and interactions of the nuclear matrix (NM), cytoskeleton and extracellular matrix. This system is a dynamic structural and functional component of the cell that maintains and coordinates cell function and gene expression. The (ER-_) is localized to the NM and studies suggest that alterations in NM proteins may influence gene expression. Three proteins (identified as cytokeratins 8, 18 and 19) present in the NM-intermediate filament (NM-IF) fraction were found to be regulated by estrogen in T5 human breast cancer cells. However, T5-PRF, estrogen-nonresponsive cells, overexpressed these three proteins compared to T5 cells, and these proteins were no longer regulated by estrogen in T5-PRF cells. Treating T5 cells with antiestrogens resulted in a significant reduction in these proteins, while no effect was seen in T5-PRF cells, supporting the conclusion that these three NM-IF proteins are regulated by estrogen in T5 human breast cancer cells and may play a role in estrogen action in human breast Comm cells. T5-PRF cells were also found to have significantly increased ligand-independent (ER-_) activity. In addition, an ER-_ mRNA variant with an inframe deletion of exons 3 and 4 was detected in T5-PRF, but not T5, human breast cancer cells. Recombinant expression of this (ER-_) variant in T5 human breast cancer cells increased estrogen-dependent and -independent reporter gene expression, suggesting that the presence of this (ER-_) mRNA variant may contribute to anestrogen-independent growth phenotype. Furthermore, T5-PRF human breast cancer cells contained elevated mitogen-activated protein kinase (MAPK) activity. The MAPK signal transduction pathway can be activated by estrogen in human breast cancer cells and may be involved in the regulation of ER-_ transcriptional activity through both ligand-dependent and independent pathways, suggesting that increased activity of MAPK may contribute to the ligand-independent activity of the ER-_ in T5-PRF cells. In conclusion, T5-PRF human breast cancer cells contain several changes compared to parental T5 cells, which may all contribute to an estrogen-nonresponsive growth phenotype and affect the transcriptional activity/regulation of the (ER-_)
    URI
    http://hdl.handle.net/1993/2208
    Collections
    • FGS - Electronic Theses and Practica [25532]

    DSpace software copyright © 2002-2016  DuraSpace
    Contact Us | Send Feedback
    Theme by 
    Atmire NV
     

     

    Browse

    All of MSpaceCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects

    My Account

    Login

    Statistics

    View Usage Statistics

    DSpace software copyright © 2002-2016  DuraSpace
    Contact Us | Send Feedback
    Theme by 
    Atmire NV