Evolution of the Perlecan/HSPG2 gene and Regulation of its Expression by Inflammatory Cytokines in Normal Tissue Models and Cancer

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dc.contributor.advisorGustin, Michael C.
dc.contributor.committeeMemberWagner, Daniel S.
dc.contributor.committeeMemberCarson, Daniel D.
dc.contributor.committeeMemberGrande-Allen, K. Jane
dc.contributor.committeeMemberFarach-Carson, Cindy
dc.creatorWarren, Curtis Robert
dc.date.accessioned2014-10-15T15:05:05Z
dc.date.available2014-10-15T15:05:05Z
dc.date.created2014-05
dc.date.issued2014-04-21
dc.date.submittedMay 2014
dc.date.updated2014-10-15T15:05:08Z
dc.description.abstractPerlecan is the large heparan sulfate proteoglycan common to all basement membranes. It has numerous functions in maintenance of BM integrity, cell signaling and scaffolding protein interactions. Perlecan accumulation is elevated in wound healing and is essential to organismal development. In this work the evolution of perlecan and its role in the simplest and most ancient animals are explored. Transcriptional regulation of the HSPG2 gene also is examined in human prostate cancer and associated stromal cells. The protein was elevated in the reactive stroma of primary prostate cancer and TNF-α was identified as the primary driver of HSPG2 expression induction in various prostate cancer, prostate stromal and bone marrow stromal cell lines. Various aspects of this response echo the fibroblastic response to wounding and tumor progression. HSPG2 homologues were found in the genomes of the cnidarian, Nematostella vectensis, and the placozoan, Trichoplax adhaerens. Thus the last common ancestor to encode a perlecan homologue is the placozoan Trichoplax adhaerens. N. vectensis perl elevation was identified as part of the gene expression profile of complex regenerating structures in the oral region of the animal following wounding. This is a conserved expression pattern of the gene which is still found in wound healing of modern mammals. These studies both demonstrate a role for perlecan in wound healing and pathological states, corroborating the hypothesis that the perlecan gene’s primary evolutionary role is to support tissues in times of remodeling.
dc.format.mimetypeapplication/pdf
dc.identifier.citationWarren, Curtis Robert. "Evolution of the Perlecan/HSPG2 gene and Regulation of its Expression by Inflammatory Cytokines in Normal Tissue Models and Cancer." (2014) Diss., Rice University. <a href="https://hdl.handle.net/1911/77575">https://hdl.handle.net/1911/77575</a>.
dc.identifier.urihttps://hdl.handle.net/1911/77575
dc.language.isoeng
dc.rightsCopyright is held by the author, unless otherwise indicated. Permission to reuse, publish, or reproduce the work beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder.
dc.subjectPerlecan
dc.subjectHSPG2
dc.subjectProstate cancer
dc.subjectTumor necrosis factor
dc.subjectTrichoplax adhaerens
dc.subjectNematostella vectensis
dc.subjectTissue regeneration
dc.titleEvolution of the Perlecan/HSPG2 gene and Regulation of its Expression by Inflammatory Cytokines in Normal Tissue Models and Cancer
dc.typeThesis
dc.type.materialText
thesis.degree.departmentBiochemistry and Cell Biology
thesis.degree.disciplineNatural Sciences
thesis.degree.grantorRice University
thesis.degree.levelDoctoral
thesis.degree.nameDoctor of Philosophy
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