Prostate cancer is still the most diagnosed cancer in man in the Western world and in this group, one of the leading causes of cancer death. CD9 protein is a member of the tetraspanin family, whose members are often down-regulated in advanced prostate cancers. The objective of our study is to decipher the role of the CD9 protein in prostate cancer progression. / We have demonstrated that over-expression of exogenous CD9 in highly tumorigenic and metastatic PC-3M-LN4 cell line did not suppress its tumorigenic and metastatic properties in vivo while it even increased its invasive properties in vitro. These data contrast with our previous study, which demonstrated that over-expression of wild type CD9 has a deleterious effect on growth properties of human PC-3 prostate cancer cells in vitro. Since CD9 is still expressed in some human prostate cancers, we linked putative inactivation of CD9 in PC-3M-LN4 cells with presence or absence of certain CD9 partners. Using co-immunopreciptation, mass-spectrometry, Bacterial two-hybrid system and Ciphergen ProteinChip technology we identified six novel CD9 protein partners, namely MORTALIN, OVCA2, HES4, GALECTIN3, RAB5A, TM4SF9. These partners could affect CD9 function in prostate cancer cells. We also detected ASPP2 protein expression only in PC-3 cells. / Pursuing the characterization of some of these partners, we showed that simultaneous over-expression of CD9 and OVCA2 in PC-3M-LN4 cells lead to mitotic catastrophe and eventually cause cell death. / Furthermore, immunocolocalization studies demonstrated that CD9 and MORTALIN interaction depend on CD9 over-expression in an appropriate cell context, putatively explaining the differential effect of CD9 in PC-3 and PC-3M-LN4 prostate cancer cells. / Overall, the data presented in this thesis demonstrated that the biological properties of CD9 protein are dependent on protein-protein interactions and cell type environment. The demonstrated interactions of CD9 with OVCA2 and MORTALIN highlighted the importance of CD9 as a potential tumor and/or metastasis suppressor gene.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.111833 |
| Date | January 2005 |
| Creators | Zvieriev, Valerii. |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Division of Experimental Medicine.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 002326443, proquestno: AAINR25292, Theses scanned by UMI/ProQuest. |
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