A molecular study on cytoskeletal proteins in the uterus during pregnancy and cancer

Abstract

The uterus has the unique ability to undergo morphological and functional changes in different biological contexts. Through the investigation of four cytoskeletal proteins, α-parvin, β-parvin, lasp-1 and palladin, during two separate events specific to the uterus, early pregnancy and endometrial carcinoma, this thesis aimed to contribute to both fields of study, whilst additionally determining comparisons and similarities in the molecular processes and proteins involved. Palladin and lasp-1 were both found to increase during the time of implantation, compared to the time of fertilisation. Lasp-1 exhibited an apical and lateral junctional localisation on both studied days of early pregnancy, however predominantly during fertilisation, indicating a potential role for the protein in the disruption of the actin terminal web and loss of adherens junctions seen during implantation. α- and β-parvin were found to play a reciprocal role during implantation, with α-parvin decreasing and β-parvin increasing during this time. Additionally, the study found that β-parvin significantly increased in the underlying stroma of the uterus during decidualisation, and that this increase was dependent on decidualisation occurring. In addition to the studies of α-parvin, β-parvin, lasp-1 and palladin in the uterus during early pregnancy, these four proteins were investigated in the glandular epithelial cells (GECs) of human endometrial cancer tissue to determine possible roles in the morphological changes seen during this event. Our results suggest a potential for the localisation of lasp-1 as an indicator for different aggressive characteristics. Phosphorylated α-parvin was additionally investigated and displayed a strong basal and apical location in low grade GECs, which was lost in type 2 serous GECs when the protein became localised to the nucleus. In combination, this thesis contributes to two different fields of study, whilst additionally elucidating similarities in the molecular processes of early pregnancy and endometrial tumorigenesis. Together this work highlights the importance of studying the role cytoskeletal proteins, α-parvin, β-parvin, lasp-1 and palladin, have in cellular changes involving morphological and proliferative transformations.