Skip Navigation



Carcinogenesis Advance Access published online on October 27, 2006
Carcinogenesis, doi:10.1093/carcin/bgl202
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow All Versions of this Article:
28/3/749    most recent
bgl202v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Kim, D. S.
Right arrow Articles by McCabe, C. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kim, D. S.
Right arrow Articles by McCabe, C. J.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2006. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org
Received May 18, 2006
Revised October 11, 2006
Accepted October 14, 2006

CARCINOGENESIS

Securin induces genetic instability in colorectal cancer by inhibiting double-stranded DNA repair activity

D. S. Kim 1, J. A. Franklyn 1, V. E. Smith 1, A. L. Stratford 1, H. N. Pemberton 1, A. Warfield 2, J. C. Watkinson 1, T. Ishmail 3, M. J. O. Wakelam 4, and C. J. McCabe 1 *

1 Division of Medical Sciences, Institute of Biomedical Research, University of Birmingham, B15 2TH, UK
2 Department of Cellular Pathology (Histopathology), University of Birmingham, UK
3 University Hospital Birmingham Trust, Birmingham, UK
4 CRUK Institute for Cancer Studies, University of Birmingham, UK

* To whom correspondence should be addressed.
C. J. McCabe, E-mail: mccabcjz{at}bham.ac.uk


  Abstract

Genetic instability is a hallmark feature of tumor development. Securin, also known as pituitary tumor transforming gene (PTTG), is a mitotic checkpoint protein which is highly expressed in numerous cancers, is associated with tumor invasiveness, and induces genetic instability (GI) in thyroid cells. We used fluorescence inter-simple sequence repeat PCR to assess genetic instability caused primarily by DNA breakage events in 19 colorectal tumors. GI values ranged significantly, with Dukes' stage C&D colorectal tumors exhibiting greater genetic instability and higher securin expression than Dukes' stage A&B tumors. Consistent with these findings, we observed a dose-dependent increase in genetic instability in HCT116 cells in response to securin over-expression, as well as in non-transformed human fibroblasts. As securin has been implicated in a novel DNA repair pathway in fission yeast, we investigated its potential role in chemotoxic DNA damage response pathways in mammalian cells, using host cell reactivation assays. Securin over-expression in HCT116 cells inhibited etoposide-induced double-stranded DNA damage repair activity, and repressed Ku heterodimer function. Additionally, we observed that securin and Ku70 showed a reciprocal cytosol-nuclear translocation in response to etoposide-induced dsDNA damage. Our data suggest that, by repressing Ku70 activity and inhibiting the non-homologous end-joining dsDNA repair pathway, securin may be a critical gene in the development of genetic instability in colorectal cancer.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 J Mol EndocrinolHome page
Y. Tong and T. Eigler
Transcriptional targets for pituitary tumor-transforming gene-1
J. Mol. Endocrinol., November 1, 2009; 43(5): 179 - 185.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Biol. CellHome page
A. G. Espina, C. Mendez-Vidal, M. A. Moreno-Mateos, C. Saez, A. Romero-Franco, M. A. Japon, and J. A. Pintor-Toro
Induction of Dlk1 by PTTG1 Inhibits Adipocyte Differentiation and Correlates with Malignant Transformation
Mol. Biol. Cell, July 15, 2009; 20(14): 3353 - 3362.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
V. Chesnokova, S. Zonis, K. Kovacs, A. Ben-Shlomo, K. Wawrowsky, S. Bannykh, and S. Melmed
p21Cip1 restrains pituitary tumor growth
PNAS, November 11, 2008; 105(45): 17498 - 17503.
[Abstract] [Full Text] [PDF]

Home page
 Endocr Relat CancerHome page
F. Salehi, K. Kovacs, B. W Scheithauer, R. V Lloyd, and M. Cusimano
Pituitary tumor-transforming gene in endocrine and other neoplasms: a review and update
Endocr. Relat. Cancer, September 1, 2008; 15(3): 721 - 743.
[Abstract] [Full Text] [PDF]

Home page
 Endocr Relat CancerHome page
C. Zhou, Y. Tong, K. Wawrowsky, S. Bannykh, I. Donangelo, and S. Melmed
Oct-1 induces pituitary tumor transforming gene expression in endocrine tumors
Endocr. Relat. Cancer, September 1, 2008; 15(3): 817 - 831.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
V. Chesnokova, S. Zonis, T. Rubinek, R. Yu, A. Ben-Shlomo, K. Kovacs, K. Wawrowsky, and S. Melmed
Senescence Mediates Pituitary Hypoplasia and Restrains Pituitary Tumor Growth
Cancer Res., November 1, 2007; 67(21): 10564 - 10572.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.