Insulin-like growth factors and their binding proteins in human colonocytes: preferential degradation of insulin-like growth factor binding protein 2 in colonic cancers.

We have compared the expression of insulin-like growth factors (IGFs) and IGF binding proteins (IGFBPs) in ten paired samples of normal and tumour colonic tissue with regard to both mRNA and protein. We have compared sensitivity of these tissues to IGF-I using primary cultures of epithelial cells of...

Descripción completa

Detalles Bibliográficos
Autores principales: Michell, N. P., Langman, M. J., Eggo, M. C.
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 1997
Materias:
Research Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2223789/
https://www.ncbi.nlm.nih.gov/pubmed/9218734
_version_ 1782149439763251200
author Michell, N. P.
Langman, M. J.
Eggo, M. C.
author_facet Michell, N. P.
Langman, M. J.
Eggo, M. C.
author_sort Michell, N. P.
collection PubMed
description We have compared the expression of insulin-like growth factors (IGFs) and IGF binding proteins (IGFBPs) in ten paired samples of normal and tumour colonic tissue with regard to both mRNA and protein. We have compared sensitivity of these tissues to IGF-I using primary cultures of epithelial cells of colonic mucosa, and we have examined the production of IGFs and IGFBPs by these cells. In the tissues, IGFBP-2 mRNA was expressed in all normal and cancer samples but other IGFBPs showed variable expression. mRNAs for IGF-I were expressed in all normal and cancer tissues but IGF-II mRNA was only detected in cancer tissue (3 out of 10). Immunostaining of sections of normal and cancer tissue was negative for IGF-I and IGF-II; IGFBP-2 was positive in 2 out of 10 cancer tissues and 7 out of 10 normal tissues; IGFBP-3 was positive in 7 out of 10 cancer tissues and 7 out of 10 normal tissues; and IGFBP-4 was positive in 5 out of 10 cancer tissues and 6 out of 10 normal tissues. In the cells in culture, cancer cells showed increased incorporation of [35S]methionine into protein and [3H]thymidine into DNA (P < 0.02) when treated with IGF-I. Western blotting of serum-free conditioned media from cells in culture showed that 8 out of 10 normal and 3 out of 10 cancer cultures produced a 32-kDa immunoreactive IGFBP-2. No IGFBP-3 was secreted by any culture but 24-kDa IGFBP-4 was found in 3 out of 10 normal and 5 out of 10 cancer tissues. Because of the discrepancy between mRNA and protein expression for IGFBP-2, degradation of native IGFBPs was assessed using tissue extracts. Colon cancer extracts were able to degrade exogenous IGFBP-2, IGFBP-3 and IGFBP-4, whereas normal tissue extracts were without effect on IGFBP-2. We conclude that IGFBPs are synthesized and secreted by cells of the colonic mucosa but that proteolysis of secreted IGFBP-2 occurs in colon cancer tissue. This selective degradation may confer a growth advantage. IMAGES:
format Text
id pubmed-2223789
institution National Center for Biotechnology Information
language English
publishDate 1997
publisher Nature Publishing Group
record_format MEDLINE/PubMed
spelling pubmed-22237892009-09-10 Insulin-like growth factors and their binding proteins in human colonocytes: preferential degradation of insulin-like growth factor binding protein 2 in colonic cancers. Michell, N. P. Langman, M. J. Eggo, M. C. Br J Cancer Research Article We have compared the expression of insulin-like growth factors (IGFs) and IGF binding proteins (IGFBPs) in ten paired samples of normal and tumour colonic tissue with regard to both mRNA and protein. We have compared sensitivity of these tissues to IGF-I using primary cultures of epithelial cells of colonic mucosa, and we have examined the production of IGFs and IGFBPs by these cells. In the tissues, IGFBP-2 mRNA was expressed in all normal and cancer samples but other IGFBPs showed variable expression. mRNAs for IGF-I were expressed in all normal and cancer tissues but IGF-II mRNA was only detected in cancer tissue (3 out of 10). Immunostaining of sections of normal and cancer tissue was negative for IGF-I and IGF-II; IGFBP-2 was positive in 2 out of 10 cancer tissues and 7 out of 10 normal tissues; IGFBP-3 was positive in 7 out of 10 cancer tissues and 7 out of 10 normal tissues; and IGFBP-4 was positive in 5 out of 10 cancer tissues and 6 out of 10 normal tissues. In the cells in culture, cancer cells showed increased incorporation of [35S]methionine into protein and [3H]thymidine into DNA (P < 0.02) when treated with IGF-I. Western blotting of serum-free conditioned media from cells in culture showed that 8 out of 10 normal and 3 out of 10 cancer cultures produced a 32-kDa immunoreactive IGFBP-2. No IGFBP-3 was secreted by any culture but 24-kDa IGFBP-4 was found in 3 out of 10 normal and 5 out of 10 cancer tissues. Because of the discrepancy between mRNA and protein expression for IGFBP-2, degradation of native IGFBPs was assessed using tissue extracts. Colon cancer extracts were able to degrade exogenous IGFBP-2, IGFBP-3 and IGFBP-4, whereas normal tissue extracts were without effect on IGFBP-2. We conclude that IGFBPs are synthesized and secreted by cells of the colonic mucosa but that proteolysis of secreted IGFBP-2 occurs in colon cancer tissue. This selective degradation may confer a growth advantage. IMAGES: Nature Publishing Group 1997 /pmc/articles/PMC2223789/ /pubmed/9218734 Text en https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/.
spellingShingle Research Article
Michell, N. P.
Langman, M. J.
Eggo, M. C.
Insulin-like growth factors and their binding proteins in human colonocytes: preferential degradation of insulin-like growth factor binding protein 2 in colonic cancers.
title Insulin-like growth factors and their binding proteins in human colonocytes: preferential degradation of insulin-like growth factor binding protein 2 in colonic cancers.
title_full Insulin-like growth factors and their binding proteins in human colonocytes: preferential degradation of insulin-like growth factor binding protein 2 in colonic cancers.
title_fullStr Insulin-like growth factors and their binding proteins in human colonocytes: preferential degradation of insulin-like growth factor binding protein 2 in colonic cancers.
title_full_unstemmed Insulin-like growth factors and their binding proteins in human colonocytes: preferential degradation of insulin-like growth factor binding protein 2 in colonic cancers.
title_short Insulin-like growth factors and their binding proteins in human colonocytes: preferential degradation of insulin-like growth factor binding protein 2 in colonic cancers.
title_sort insulin-like growth factors and their binding proteins in human colonocytes: preferential degradation of insulin-like growth factor binding protein 2 in colonic cancers.
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2223789/
https://www.ncbi.nlm.nih.gov/pubmed/9218734
work_keys_str_mv AT michellnp insulinlikegrowthfactorsandtheirbindingproteinsinhumancolonocytespreferentialdegradationofinsulinlikegrowthfactorbindingprotein2incoloniccancers
AT langmanmj insulinlikegrowthfactorsandtheirbindingproteinsinhumancolonocytespreferentialdegradationofinsulinlikegrowthfactorbindingprotein2incoloniccancers
AT eggomc insulinlikegrowthfactorsandtheirbindingproteinsinhumancolonocytespreferentialdegradationofinsulinlikegrowthfactorbindingprotein2incoloniccancers

Ejemplares similares