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dc.contributor.authorZhu, Shu Junen
dc.date2010-01-20 12:37:55.613
dc.date.accessioned2015-01-20T16:21:34Z
dc.date.available2015-01-20T16:21:34Z
dc.date.issued2015-01-20
dc.identifier.urihttp://hdl.handle.net/1974/12701
dc.descriptionThesis (Master, Pathology & Molecular Medicine) -- Queen's University, 2010-01-20 12:37:55.613en
dc.description.abstractThe RET receptor has diverse roles in development and disease, modulating proliferation, survival, and migration of cells. Ligand-independent constitutively active forms of RET can lead to thyroid neoplasia. Missense mutations are causative agents in multiple endocrine neoplasia type 2 (MEN 2), featuring medullary thyroid carcinoma (MTC), whereas RET fusion oncoproteins generated by gene rearrangements are associated with papillary thyroid carcinoma (PTC). In gene expression screens, interleukin-11 was identified as a RET-responsive gene. We sought to characterize the expression of IL-11 in response to activation of the RET receptor, and determine how IL-11 might contribute to RET-mediated cell behaviours. Analysis of HEK293 cells expressing RET, by qRT-PCR and ELISA, established that activation of wild-type RET, MEN 2- and PTC-associated RET upregulated IL-11 transcription and secretion. RET induction of IL-11 gene expression appears to be affected directly and indirectly, and is dependent on activation of the RAS/ERK1/2 signalling pathway. Examination of thyroid carcinoma cell lines with activated RET indicated that PTC-derived TPC-1 cells express IL-11. Addition of exogenous IL-11 stimulated STAT3 phosphorylation in thyroid cancer cell lines, though IL-11 did not affect the proliferation, adhesion, or survival against anoikis in the cells. Immunohistochemical analyses of human thyroid tissues revealed that RET, IL-11, and IL-11Rα are expressed in thyroid cells of the normal thyroid, MTC and PTC. Expression of the three molecules was also detected in immune cell infiltrates in PTC. Although we were unable to confirm that the autocrine IL-11 stimulation might affect the behaviour of thyroid cancer cells, it is likely that IL-11 exerts paracrine immunomodulatory effects, and acts downstream of RET in normal biological processes.en
dc.language.isoengen
dc.relation.ispartofseriesCanadian thesesen
dc.rightsThis publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.en
dc.subjectRETen
dc.subjectIL-11en
dc.titleRET receptor activation targets expression of the pleiotropic cytokine interleukin-11en
dc.typethesisen
dc.description.degreeM.Sc.en
dc.contributor.supervisorMulligan, Lois M.en
dc.contributor.departmentPathology and Molecular Medicineen
dc.degree.grantorQueen's University at Kingstonen


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