AbstractsBiology & Animal Science

Breast cancer is the most frequently diagnosed and the second leading cause of cancer deaths in Canadian women. The most morbid and deadly feature of the disease is the emergence of metastases. Breast cancer progression is a consequence of disruption of normal cell organization, polarity, and cell-cell adhesion, which allow cells to become more motile and invasive. Atypical protein kinase C iota (aPKCἰ) functions as an oncogene and is found to be elevated in lung adenocarcinoma, chronic myelogenous leukaemia, non-small cell lung cancer cell lines, ovarian, pancreatic, colon and breast cancers. In addition, several studies demonstrate an important role for aPKCι in promoting tumour cell invasion and the subsequent formation of metastases in a number of human cancers. Also, aPKCι was suggested to be involved in the extracellular matrix degradation in breast cancer. However, the exact mechanisms by which aPKCι promotes breast cancer cell invasion remain to be elucidated.The purpose of this thesis is to establish the role of aPKCἰ in breast cancer invasion and metastasis. To achieve this, a 3D collagen in vitro assay was chosen to examine the effect of aPKCἰ overexpression on breast cancer cell invasiveness, morphology, the formation of cellular protrusions. I also investigated the potential molecular mechanisms of aPKCι involvement in breast cancer cell invasion. The work in this thesis demonstrates that the aPKCἰ overexpressing cells are capable of invading further distances into the surrounding collagen matrix and possessed higher speed than the control cell line. Furthermore, these cells changed morphology, as characterized by the formation of multiple protrusions. Additionally, the number of cellular protrusions was found to correlate with the cell invasion velocity. Finally, a study of the the molecular pathway underlying the role of aPKCἰ in breast cancer cell invasion was initiated. Le cancer du sein est le cancer le plus fréquemment diagnostiqué et la deuxième cause de décès du cancer chez les femmes canadiennes. La caractéristique la plus morbide et mortelle de la maladie est la formation des métastases. La progression du cancer du sein est une conséquence de la perturbation de l'organisation cellulaire normale, de la polarité et de l'adhérence cellule à cellule, ce qui permet aux cellules d'être plus mobiles et invasives. La protéine kinase C atypique iota (aPKCἰ) agit comme un oncogène et se trouve en taux élevé dans l'adénocarcinome du poumon, la leucémie myéloïde chronique, les lignées cellulaires de cancer bronchique non à petites cellules, et les cancers de l'ovaire, du pancréas, du côlon et du sein. Également, plusieurs études ont démontré que aPKCι joue un rôle important dans la promotion de l'invasion des cellules tumorales et la formation subséquente des métastases dans un certain nombre de cancers humains. En outre, il a été suggéré que aPKCι est impliqué dans la dégradation de la matrice extra-cellulaire dans le contexte de cancer du sein. Cependant, il reste à élucider le mécanisme exact par…