Research@StAndrews
 
The University of St Andrews

Research@StAndrews:FullText >
Medicine (School of) >
Medicine >
Medicine Theses >

Please use this identifier to cite or link to this item: http://hdl.handle.net/10023/900
This item has been viewed 10 times in the last year. View Statistics

Files in This Item:

File Description SizeFormat
The full text of this document is not available.pdfmain thesis2.61 kBAdobe PDFView/Open
Title: The effects of leptomycin B on HPV-infected cells
Authors: Jolly, Carol E
Supervisors: Herrington, C. Simon
Keywords: Human papillomavirus
Cervical cancer
Leptomycin B
Apoptosis
P53
Issue Date: 2008
Abstract: Cervical cancer is a major cause of death in women and is strongly associated with infection by human papillomavirus (HPV). Integration of HPV is thought to form a key step in the formation of cancer, and is thought to involve the upregulation of HPV E6 and E7 due to the loss of E2 transcriptional control. Leptomycin B (LMB), a nuclear export inhibitor, has previously been shown to induce apoptosis in HPV-containing cancer cell lines and HPV 16 E7 or E6/E7 transduced primary keratinocytes, but not in normal cells. This thesis shows that LMB can induce apoptosis and a reduction in the colony survival of derivatives of the W12 cell line that contain HPV 16 in either episomal or integrated form. The HPV genome status, including variations in viral integration type, appears to influence the cumulative and temporal pattern of LMB-induced apoptosis. The effects of LMB were also apparent in cells grown in organotypic raft culture, with differences in behaviour again apparent between cells containing episomal and integrated HPV. As previously noted, treatment with LMB was associated with increased expression of the cell regulators p53 and p21; however, the induction of apoptosis was not dependent upon transcriptionally active p53. It is therefore likely that induction and mediation of LMB-induced apoptosis occurs via alternative, currently unidentified, pathways. These findings suggest that LMB can induce apoptosis in keratinocytes containing HPV 16 in either episomal or integrated form, with genome status and potentially lesion grade likely to influence the response of HPV-associated anogenital lesions to LMB treatment.
URI: http://hdl.handle.net/10023/900
Type: Thesis
Publisher: University of St Andrews
Appears in Collections:Medicine Theses



This item is protected by original copyright

This item is licensed under a Creative Commons License
Creative Commons

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

 

DSpace Software Copyright © 2002-2012  Duraspace - Feedback
For help contact: Digital-Repository@st-andrews.ac.uk | Copyright for this page belongs to St Andrews University Library | Terms and Conditions (Cookies)