Nck is as an adaptor protein previously implicated in actin cytoskeleton reorganization and by our laboratory, in translation and cell response to stress. Our primary objective was to determine the expression levels of Nck isotypes (Nck-1 and Nck-2) during cancer progression. We have performed western blot analysis of the Nck isotypes expression levels profile in various human cancer cell lines, at different stages of progression. Our data show significantly higher expression levels of Nck-2 protein in metastatic melanomas compared to non-metastatic melanomas and normal melanocytes. Using semi-quantitative RT-PCR, we demonstrated that this increase in Nck-2 expression can be also seen at the transcriptional level. The Ras/RAF/MEK/ERK pathway is often spontaneously activated in melanomas causing hyperactivation of ERK. By downregulating the expression of Nck-2 using siRNA, we have established a strong correlation between increased expression levels of Nck-2 and activated ERK. Furthermore, we have demonstrated the involvement of Nck-2 in cell proliferation and adhesion in metastatic melanomas, revealing that Nck-2 acts as a new player in this disease.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.101852 |
| Date | January 2007 |
| Creators | Ismail, Salma. |
| 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 Physiology.) |
| Rights | © Salma Ismail, 2007 |
| Relation | alephsysno: 002653698, proquestno: AAIMR38403, Theses scanned by UMI/ProQuest. |
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