Skip to Main Content
 

Global Search Box

 
 
 
 

ETD Abstract Container

Abstract Header

Regulation of the PDGF genes and translocation patterns of protein kinase C isotypes in human glioblastomas

Misra-Press, Anita

Abstract Details

1991, Doctor of Philosophy, Case Western Reserve University, Biochemistry.
PDGF-A mRNA was expressed in all glioblastoma cell lines and in normal human glial cells. In contrast, PDGF-B mRNA was absent from normal glial cells but was expressed in the majority of glioblastoma cell lines. These observations supported a role for PDGF-B in the autocrine growth stimulation of glioblastomas. The expression of both the PDGF genes was stimulated by phorbol 12-myristate 13-acetate (PMA), transforming growth factor beta (TGF-β), or increases in intracellular calcium. Previous results had shown the TGF-β mediated pathway towards PDGF gene expression to be independent of the PKC pathway. dB-cAMP was able to abolish the stimulation of both these genes by PMA or TGF-β. aThus, the protein kinase A (PKA) transduction pathway had a dominant inhibitory effect on the PKC and TGF-β mediated pathways toward induction of the PDGF genes. dB-cAMP exhibited a strong inhibitory effect on basal levels of PDGF-B expression while its effect on PDGF-A was weak. dB-cAMP caused an exponential decay of PDGF-B mRNA with a half life of decay similar to its half life with actinomycin D. The primary mechanism by which dB-cAMP exerted this negative effect was by an inhibition of PDGF-B gene transcription. The ability of glioblastoma cells to differentiate in response to dB-cAMP appeared to correlate with inhibition of PDGF-B transcription. PKC isotypes expressed in human glioblastoma cells were also examined. PCK-α mRNA was expressed in all 8 glioblastoma cell lines and in normal glial cells, unlike PKC-β which was not expressed in any. aPMA translocated PKC-α from its normal cytosolic location to both the plasma membrane and the nucleus in A172 cells and preferentially to the nucleus in A2781 cells. The translocation to the nucleus and plasma membrane occurred within 10 minutes of PMA exposure. Down-regulation of PKC-α was observed on prolonged PMA treatment. The PMA-induced nuclear translocation of PKC-α was accompanied by an increased phosphorylation of nuclear envelope proteins. TGF-β or dB-cAMP were also able to cause changes in the amounts and distribution of PKC-α and γ in the different subcellular locations. These results demonstrate "cross-talk" between separate signaling systems
David Goldthwait (Advisor)
267 p.

Recommended Citations

Citations

  • Misra-Press, A. (1991). Regulation of the PDGF genes and translocation patterns of protein kinase C isotypes in human glioblastomas [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1059152679

    APA Style (7th edition)

  • Misra-Press, Anita. Regulation of the PDGF genes and translocation patterns of protein kinase C isotypes in human glioblastomas. 1991. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1059152679.

    MLA Style (8th edition)

  • Misra-Press, Anita. "Regulation of the PDGF genes and translocation patterns of protein kinase C isotypes in human glioblastomas." Doctoral dissertation, Case Western Reserve University, 1991. http://rave.ohiolink.edu/etdc/view?acc_num=case1059152679

    Chicago Manual of Style (17th edition)