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Abnormal expression and structural modification of the insulin-like growth-factor-II gene in human colorectal tumors
Abstract:
The insulin-like growth factor II (IGF-II) is a small protein implicated in fetal growth and development. It may play a role in the neoplastic process. The IGF-II gene is located on the short arm of chromosome II near insulin and c-Ha-ras I genes. Three distinct promoters control the transcription of this gene, leading to different IGF-II mRNA species. We have analyzed 21 human colorectal tumors and found overexpression of IGF-II in 6 of them (30%). When compared with expression in normal adjacent tissues, IGF-II mRNA increase in these tumors was either moderate (2- to 15-fold) or very marked (200- to 800-fold). In situ hybridization experiments confirmed that high IGF-II mRNA amounts were localized in cancer cells of the tumors overexpressing the IGF-II gene. In addition, DNA analysis revealed a structural modification of one IGF-II locus in one tumor characterized by very high IGF-II mRNA.
Insights
Insulin-like growth factor II (IGF-II) is overexpressed in 30% of colorectal tumors, potentially contributing to cancer development. This overexpression, particularly marked in some cases, was localized to cancer cells, suggesting a role in neoplastic processes.
Area of Science:
- Molecular Biology
- Genetics
- Oncology
Background:
- Insulin-like growth factor II (IGF-II) is a protein crucial for fetal growth.
- IGF-II may be involved in cancer development.
- The IGF-II gene is located on chromosome 11 and regulated by three promoters.
Purpose of the Study:
- To investigate the role of IGF-II in human colorectal tumors.
- To quantify IGF-II gene expression in colorectal cancer.
- To determine the cellular localization of IGF-II mRNA in tumors.
Main Methods:
- Analysis of 21 human colorectal tumors.
- Quantitative assessment of IGF-II mRNA levels via Northern blot or similar techniques.
- In situ hybridization to localize IGF-II mRNA within tumor tissues.
- DNA analysis to identify structural modifications in the IGF-II gene locus.
Main Results:
- Overexpression of IGF-II was detected in 6 out of 21 (30%) colorectal tumors.
- IGF-II mRNA levels showed moderate (2- to 15-fold) or marked (200- to 800-fold) increases compared to normal adjacent tissues.
- In situ hybridization confirmed high IGF-II mRNA levels were concentrated within cancer cells.
- One tumor with very high IGF-II mRNA exhibited a structural modification at the IGF-II locus.
Conclusions:
- IGF-II is frequently overexpressed in colorectal tumors.
- The overexpression of IGF-II is localized to cancer cells, supporting its role in colorectal neoplasia.
- Structural alterations in the IGF-II gene locus may contribute to its overexpression in some tumors.