• Find People
  • Campus Map
  • PiratePort
  • A-Z
    • About
    • Submit
    • Browse
    • Login
    View Item 
    •   ScholarShip Home
    • Division of Health Sciences
    • Brody School of Medicine
    • Biochemistry and Molecular Biology
    • View Item
    •   ScholarShip Home
    • Division of Health Sciences
    • Brody School of Medicine
    • Biochemistry and Molecular Biology
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of The ScholarShipCommunities & CollectionsDateAuthorsTitlesSubjectsTypeDate SubmittedThis CollectionDateAuthorsTitlesSubjectsTypeDate Submitted

    My Account

    Login

    Statistics

    View Google Analytics Statistics

    Effects of Exogenous and Autocrine Growth Hormone (hGH) on Prostate Cancer Cell Function

    Thumbnail
    View/ Open
    Nakonechnaya_ecu_0600D_10645.pdf (2.860Mb)

    Show full item record
    Author
    Nakonechnaya, Alena O.
    Abstract
    Human growth hormone (hGH) is a major product of the anterior pituitary. In addition to its endocrine activities, hGH overexpression in extra-pituitary tissues has been correlated with the oncogenic behavior of these tissues, where it has been shown to function in an autocrine manner. hGH and its receptor (hGHR) have been shown to be expressed in prostate cancer (PCa) cells. Our preliminary work showed that expression of hGH and hGHR mRNA was elevated in PCa cell lines compared to normal prostate-derived epithelial cell lines, suggesting hypersensitivity of these cells to exogenous hGH, or establishment of autocrine signaling. Addressing these questions showed that PCa cells are sensitive to physiological concentrations of hGH, which can increase cell proliferation depending on the cell line. As shown in LNCaP cells, exogenous hGH increased DNA synthesis, whereas endogenous autocrine hGH resulted in decreased DNA synthesis and increased apoptosis. Investigation of the hGH signaling mechanisms in LNCaP cells revealed that autocrine hGH affected hGHR trafficking, resulting in the sequestering of hGHR inside the cell, likely in the Golgi apparatus and endoplasmic reticulum in the contrast with exogenous hGH which activated canonical signaling pathways. However, both exogenous and endogenous hGH increased LNCaP cell motility. This effect was accompanied by increased actin polymerization, which indicates a potential direct action of hGH signaling on the motility mechanism in PCa cells. Investigation of the molecular mechanisms of hGH-N gene activation in LNCaP cells compared to rat somatotropes and normal prostate epithelial cells revealed multiple cis activities in the 5'-flanking hGH-N promoter and corresponding DNA-binding activities were observed in PCa cells that were absent in normal prostate-derived cell lines. This suggests that hGH-N expression in LNCaP cells may be differentially regulated compared to normal prostate epithelium and pituitary somatotropes. Taken together, these studies indicate a hGH-N transcriptional activation mechanism associated with prostate cancer cells, and the responsiveness of prostate cancer cells to hGH. However, these results also suggest a distinction between the effects of endocrine and autocrine hGH, which may be due to the unique effect of autocrine hGH on hGHR trafficking.
    URI
    http://hdl.handle.net/10342/3897
    Subject
     Chemistry, Biochemistry; Biology, Molecular; Exogenous vs. Autocrine; Growth hormone; Prostate--Cancer; Molecular biology; Biochemistry 
    Date
    2012
    Citation:
    APA:
    Nakonechnaya, Alena O.. (January 2012). Effects of Exogenous and Autocrine Growth Hormone (hGH) on Prostate Cancer Cell Function (Doctoral Dissertation, East Carolina University). Retrieved from the Scholarship. (http://hdl.handle.net/10342/3897.)

    Display/Hide MLA, Chicago and APA citation formats.

    MLA:
    Nakonechnaya, Alena O.. Effects of Exogenous and Autocrine Growth Hormone (hGH) on Prostate Cancer Cell Function. Doctoral Dissertation. East Carolina University, January 2012. The Scholarship. http://hdl.handle.net/10342/3897. May 19, 2022.
    Chicago:
    Nakonechnaya, Alena O., “Effects of Exogenous and Autocrine Growth Hormone (hGH) on Prostate Cancer Cell Function” (Doctoral Dissertation., East Carolina University, January 2012).
    AMA:
    Nakonechnaya, Alena O.. Effects of Exogenous and Autocrine Growth Hormone (hGH) on Prostate Cancer Cell Function [Doctoral Dissertation]. Greenville, NC: East Carolina University; January 2012.
    Collections
    • Biochemistry and Molecular Biology
    • Dissertations
    Publisher
    East Carolina University

    xmlui.ArtifactBrowser.ItemViewer.elsevier_entitlement

    East Carolina University has created ScholarShip, a digital archive for the scholarly output of the ECU community.

    • About
    • Contact Us
    • Send Feedback