JCP

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS REGISTER
[Advanced]

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this link to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Add article to my folders
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bennett, M W
Right arrow Articles by Shanahan, F
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bennett, M W
Right arrow Articles by Shanahan, F
J Clin Pathol 2001; 54:598-604
© 2001 Journal of Clinical Pathology

Fas ligand upregulation is an early event in colonic carcinogenesis

M W Bennett1, J O'Connell1, A Houston1, J Kelly1, G C O'Sullivan2, J K Collins1, F Shanahan1

1 Department of Medicine, University College Cork, Cork, Ireland
2 Department of Surgery, University College Cork

Professor Shanahan, Department of Medicine, Clinical Sciences Building, University Hospital, Cork, Ireland Fshanahan{at}ucc.ie Background/Aims—Fas ligand (FasL) is a mediator of apoptosis via the Fas receptor (Fas/CD95/APO-1). Normal colonic epithelium expresses Fas, and appears to be relatively sensitive to Fas mediated apoptosis. Colonic adenocarcinomas coexpress FasL and Fas without undergoing widespread apoptosis. This study investigates the expression of FasL in colonic carcinogenesis from the earliest stages of the adenoma–carcinoma sequence.

Methods—FasL expression was determined in colonic adenomas (n = 38) of varying degrees of dysplasia and histological type by immunohistochemistry. Adenomas that contained areas of carcinomatous change were included (n = 12 of 38). Normal colonic epithelium (n = 10), hyperplastic polyps (n = 8), and serrated adenomas (n = 3) from patients without colonic adenocarcinomas were used for comparison. Cell death was detected in situ in adenomas using TUNEL (terminal transferase mediated dUTP nick end labelling).

Results—In normal colonic epithelium and hyperplastic polyps, FasL expression was restricted to the luminal surface of the crypts, where Fas–FasL coexpression was coincident with a high frequency of TUNEL positive epithelial cells. All adenomas (n = 38) had an altered distribution of positive FasL staining; FasL expression was found in most cells (> 70% of neoplastic cells). Expression of Fas was also detected throughout the adenomas, but coexpression of FasL and Fas was not associated with TUNEL positivity in most cells.

Conclusions—FasL upregulation occurs early in the adenoma–carcinoma sequence of colon carcinogenesis, and is evident at the level of mild dysplasia. The lack of pronounced apoptosis in areas of adenomas coexpressing Fas and FasL suggests that colonocytes acquire resistance to Fas mediated apoptosis early in the transformation process.

Key Words: Fas (CD95/APO-1) • Fas ligand • colon • adenoma




This article has been cited by other articles:


Home page
J. Biol. Chem.Home page
C. Steinmann, M. L. Landsverk, J. M. Barral, and D. Boehning
Requirement of Inositol 1,4,5-Trisphosphate Receptors for Tumor-mediated Lymphocyte Apoptosis
J. Biol. Chem., May 16, 2008; 283(20): 13506 - 13509.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
C. Nadal, J. Maurel, R. Gallego, A. Castells, R. Longaron, M. Marmol, S. Sanz, R. Molina, M. Martin-Richard, and P. Gascon
FAS/FAS Ligand Ratio: A Marker of Oxaliplatin-Based Intrinsic and Acquired Resistance in Advanced Colorectal Cancer
Clin. Cancer Res., July 1, 2005; 11(13): 4770 - 4774.
[Abstract] [Full Text] [PDF]


Home page
CarcinogenesisHome page
C. L. Crowley-Weber, C. M. Payne, M. Gleason-Guzman, G. S. Watts, B. Futscher, C. N. Waltmire, C. Crowley, K. Dvorakova, C. Bernstein, M. Craven, et al.
Development and molecular characterization of HCT-116 cell lines resistant to the tumor promoter and multiple stress-inducer, deoxycholate
Carcinogenesis, December 1, 2002; 23(12): 2063 - 2080.
[Abstract] [Full Text] [PDF]


Home page
Biol. Reprod.Home page
J. C. Chen, J.-H. Lin, L.-S. Wu, Y.-F. Tsai, T. H. Su, C. J. Chen, and T. J. Chen
Luteotropic Roles of Prolactin in Early Pregnant Hamsters
Biol Reprod, July 1, 2002; 67(1): 8 - 13.
[Abstract] [Full Text] [PDF]


Home page
J. Clin. Pathol.Home page
C A Rubio, B Jacobsson, M W Bennett, J O'Connell, A Houston, J Kelly, J K Collins, F Shanahan, and G C O'Sullivan
The Fas-FasL system and colorectal tumours
J. Clin. Pathol., July 1, 2002; 55(7): 559 - 559.
[Full Text] [PDF]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS REGISTER
Journal of Clinical Pathology Molecular Pathology
Terms and conditions relating to subscriptions purchased online  ¦  Website terms and conditions  ¦  Privacy policy
Copyright © 2001 by the BMJ Publishing Group Ltd & Association of Clinical Pathologists.