SFE2002 Poster Presentations Cytokines and growth factors (7 abstracts)
IGFBP-3 mRNA expression is reduced in normal colonic mucosa of colorectal patients with colorectal cancer compared to mucosa from non cancer patients
BW Ogunkolade 1 , P Kelly P 1 , S Khalaf 1 , PD Fairclough 2 , R Li 3 , S Ahmed 3 , RL Hands 3 , SA Bustin 3 & PJ Jenkins 1
1Department of Endocrinology, St. Bartholomew's and The Royal London Queen Mary School of Medicine and Dentistry, London, UK; 2Department of Gastroenterology, St. Bartholomew's and The Royal London Queen Mary School of Medicine and Dentistry, London, UK; 3Academic Department of Surgery, St. Bartholomew's and The Royal London Queen Mary School of Medicine and Dentistry, London, UK.
Background:
Circulating levels of IGFBP-3 are inversely associated with the risk of developing colorectal cancers (CRC). In addition to modulating IGF bioavailability, IGFBP-3 also exerts independent pro-apoptotic effects. Furthermore, the mode of action of several apoptotic and antiproliferative agents, including vitamin D, has been shown to involve induction of IGFBP-3.
Aims:
To quantitate and compare IGFBP-3 mRNA expression in normal colonic biopsies and paired colonic cancer and resection margin samples.
Methods:
This study was approved by the local Ethical Committee and informed consent obtained from each patient before surgery.
Total RNA was extracted from samples from (i) colonic tumour, (ii) paired normal resection margin (n=53) and (iii) normal colonic biopsies obtained at colonoscopy from patients without cancer( n=50).
Absolute mRNA levels were quatitated by real-time RT-PCR assay using IGFBP-3 sequence-specific primers.
Results:
IGFBP-3 mRNA expression was absent in 61% of normal resection colon samples compared to 6% of cancers (p<0.0001) and 5% of normal biopsies (p<0.0001).
Overall, median mRNA levels were significantly higher in the tumours than in the paired resection normal samples (2.1 x106 vs. 2x101 copies per microgram total RNA respectively; Mann Whitney U test p<0.0001). However, there was no significant difference in median IGFBP-3 mRNA levels between the tumour samples and normal biopsies from patients without cancer (2.1 x106 vs 6.4 x105 copiesper microgram total RNA respectively).
IGFBP-3 levels did not correlate with IGF-1mRNA levels in any of the 3 groups, but there was significant correlation with IGF-1R in both the normal biopsies (r=0.6; p<0.0001) and resection margins (r=0.5; p< 0.005).
Conclusion:
The decreased or absent expression of the pro-apoptotic IGFBP-3 in adjacent normal colonic mucosa from patients with colorectal cancer compared to the cancer itself or normal colon from patient without cancer suggest either downregulation of IGFBP-3 due to tumour field effect or alternatively, a primary phenomenon in patients who develop colorectal cancer.
Article tools
My recent searches
My recently viewed abstracts
Authors
Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
© Bioscientifica 2024 |
Privacy policy |
Cookie settings
BiosciAbstracts
Bioscientifica Abstracts is the gateway to a series of products that provide a permanent, citable record of abstracts for biomedical and life science conferences.
Find out more