Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
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 ISI Web of Science
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 arrow Search for citing articles in:
ISI Web of Science (16)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Collard, T.J.
Right arrow Articles by Williams, A.C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Collard, T.J.
Right arrow Articles by Williams, A.C.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Carcinogenesis, Vol. 24, No. 3, 393-401, March 2003
© 2003 Oxford University Press

CANCER BIOLOGY

Transcriptional upregulation of the insulin-like growth factor binding protein IGFBP-3 by sodium butyrate increases IGF-independent apoptosis in human colonic adenoma-derived epithelial cells

T.J. Collard1, M. Guy1, A.J. Butt2, C.M. Perks3, J.M.P. Holly3, C. Paraskeva1 and A.C. Williams1,4

1 CRC Colorectal Tumour Biology Research Group, Department of Pathology and Microbiology, School of Medical Sciences, University of Bristol, University Walk, Bristol BS8 1TD, UK,
2 Kolling Institute of Medical Research, University of Sydney, Royal North Shore Hospital, St Leonards, NSW 2065, Australia and
3 Department of Surgery, Bristol Royal Infirmary, Bristol BS2 8HW, UK

Sodium butyrate (NaBt) and the pro-apoptotic IGFBP-3 protein, expressed at the top of the normal colonic crypt, have both been implicated in the regulation of apoptosis in colonic epithelial cells. Recent studies in human breast and hepatic cell lines have shown that NaBt can transcriptionally upregulate IGFBP-3 expression. However, the role of butyrate in the regulation of IGFBP-3 expression in the colon is less clear, with reports of both up- and downregulation of the IGFBP-3 protein in colorectal cancer cell lines. In this study we have shown that the level of IGFBP-3 protein expression in colonic epithelial cells correlates with the p53 status of the cells; wildtype p53 cells secrete higher levels of IGFBP3 protein than mutant p53 cell lines. Data presented shows that, when treated with a dose of NaBt that induced significant apoptosis (4 mM for 48 h), there was an upregulation of IGFBP-3 protein in both wildtype and mutant p53 expressing cell lines. The NaBt-induced increase in secreted IGFBP-3 protein was associated with transcriptional upregulation of the IGFBP-3 gene. Using a transfected derivative of the S/RG/C2 adenoma-derived cell line, which stably expressed exogenous IGFBP-3 protein at levels equivalent to that secreted by the 4 mM NaBt-treated parental line (1–3 ng/106 cells), we have shown a >2-fold increase in the sensitivity of the cells to NaBt-induced apoptosis when compared with the vector control and parental cell lines. Furthermore, inhibition of the secreted IGFBP-3 protein, by addition of neutralizing antibodies, resulted in a significant decrease in NaBt-induced apoptosis. These data suggest that IGFBP-3 may act as a positive regulator of NaBt-induced apoptosis in colonic epithelial cells, and represents a potentially important mechanism whereby the sensitivity of colonic epithelial cells to NaBt-induced apoptosis can be increased.


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
 Endocr Relat CancerHome page
P J Jenkins, S Khalaf, W Ogunkolade, K McCarthy, T David, R E Hands, D Davies, and S A Bustin
Differential expression of IGF-binding protein-3 in normal and malignant colon and its influence on apoptosis
Endocr. Relat. Cancer, December 1, 2005; 12(4): 891 - 901.
[Abstract] [Full Text] [PDF]

Home page
 Reproductive SciencesHome page
E. Smid-Koopman, L. C. M. Kuhne, E. E. Hanekamp, S. C.J.P. Gielen, P. E. De Ruiter, J. A. Grootegoed, T. J.M. Helmerhorst, C. W. Burger, A. O. Brinkmann, F. J. Huikeshoven, et al.
Progesterone-Induced Inhibition of Growth and Differential Regulation of Gene Expression in PRA- and/or PRB-Expressing Endometrial Cancer Cell Lines
Reproductive Sciences, May 1, 2005; 12(4): 285 - 292.
[Abstract] [PDF]

Home page
 Clin. Cancer Res.Home page
Y. H. Ibrahim and D. Yee
Insulin-Like Growth Factor-I and Breast Cancer Therapy
Clin. Cancer Res., January 15, 2005; 11(2): 944s - 950s.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Epidemiol. Biomarkers Prev.Home page
H.-L. Wong, K. DeLellis, N. Probst-Hensch, W.-P. Koh, D. Van Den Berg, H.-P. Lee, M. C. Yu, and S. A. Ingles
A New Single Nucleotide Polymorphism in the Insulin-Like Growth Factor I Regulatory Region Associates with Colorectal Cancer Risk in Singapore Chinese
Cancer Epidemiol. Biomarkers Prev., January 1, 2005; 14(1): 144 - 151.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
A. Maitra, D. E. Hansel, P. Argani, R. Ashfaq, A. Rahman, A. Naji, S. Deng, J. Geradts, L. Hawthorne, M. G. House, et al.
Global Expression Analysis of Well-Differentiated Pancreatic Endocrine Neoplasms Using Oligonucleotide Microarrays
Clin. Cancer Res., December 1, 2003; 9(16): 5988 - 5995.
[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.