This thesis explores the role of an adhesion protein, CD44, in the biology of colon cancer. CD44 glycoprotein is a main extracellular receptor for hyaluronic acid. A single CD44 gene composed of 20 exons encodes a variety of isoforms due to alternative splicing of 10 middle exons. Overexpression of CD44 and appearance of abnormal isoforms containing products of variant exons have been implicated in the origin and progression of cancer, including human colon carcinoma. / Of two main parts comprising the dissertation, the first one ("CD44 and the adhesion of neoplastic cells" by Z. Rudzki and S. Jothy) reviews the current state of knowledge on CD44, emphasizing its role in neoplastic processes. The second part ("Changes in CD44 expression during carcinogenesis of the mouse colon" by Z. Rudzki, L. LeDuy and S. Jothy) reports an experimental study of CD44 expression in a murine model of colon cancer. The tumors were induced by subcutaneous injections of a colon--specific carcinogen (1,2-dimethylhydrazine). CD44 expression was studied by RT-PCR/Southern blot and immunohistochemistry. The CD44 transcripts were generally strongly overexpressed in tumors compared with normal colon. Both neoplastic and normal colon samples exhibited the same complex array of transcript bands representing the standard molecule (CD44s) and its variant isoforms. Immunohistochemistry revealed marked heterogeneity of tumor staining, contrasting with a rather uniform mRNA overexpression. There was a significant tendency towards the progressive loss of CD44 immunoreactivity in larger and invading tumors. It is concluded that CD44 isoforms are globally overexpressed at an early, premacroscopic stage of colonic carcinogenesis. Expression of CD44 in the murine model of colon cancer shows some similarities to its human counterpart.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.27903 |
| Date | January 1997 |
| Creators | Rudzki, Zbigniew. |
| Contributors | Jothy, Serge (advisor) |
| 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 | Master of Science (Department of Pathology.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001601425, proquestno: MQ37162, Theses scanned by UMI/ProQuest. |
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