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.en_US
dc.contributor.committeeMemberWagner, Daniel S.en_US
dc.contributor.committeeMemberCarson, Daniel D.en_US
dc.contributor.committeeMemberGrande-Allen, K. Janeen_US
dc.contributor.committeeMemberFarach-Carson, Cindyen_US
dc.creatorWarren, Curtis Roberten_US
dc.date.accessioned2014-10-15T15:05:05Zen_US
dc.date.available2014-10-15T15:05:05Zen_US
dc.date.created2014-05en_US
dc.date.issued2014-04-21en_US
dc.date.submittedMay 2014en_US
dc.date.updated2014-10-15T15:05:08Zen_US
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.en_US
dc.format.mimetypeapplication/pdfen_US
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>.en_US
dc.identifier.urihttps://hdl.handle.net/1911/77575en_US
dc.language.isoengen_US
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.en_US
dc.subjectPerlecanen_US
dc.subjectHSPG2en_US
dc.subjectProstate canceren_US
dc.subjectTumor necrosis factoren_US
dc.subjectTrichoplax adhaerensen_US
dc.subjectNematostella vectensisen_US
dc.subjectTissue regenerationen_US
dc.titleEvolution of the Perlecan/HSPG2 gene and Regulation of its Expression by Inflammatory Cytokines in Normal Tissue Models and Canceren_US
dc.typeThesisen_US
dc.type.materialTexten_US
thesis.degree.departmentBiochemistry and Cell Biologyen_US
thesis.degree.disciplineNatural Sciencesen_US
thesis.degree.grantorRice Universityen_US
thesis.degree.levelDoctoralen_US
thesis.degree.nameDoctor of Philosophyen_US
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