Soluble IGF2 receptor rescues Apc(Min/+) intestinal adenoma progression induced by Igf2 loss of imprinting.
The potent growth-promoting activity of insulin-like growth factor-II (IGF-II) is highly regulated during development but frequently up-regulated in tumors. Increased expression of the normally monoallelic (paternally expressed) mouse (Igf2) and human (IGF2) genes modify progression of intestinal ad...
| Egile Nagusiak: | , , , , , |
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| Formatua: | Journal article |
| Hizkuntza: | English |
| Argitaratua: |
2006
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| _version_ | 1826288934244581376 |
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| author | Harper, J Burns, J Foulstone, E Pignatelli, M Zaina, S Hassan, A |
| author_facet | Harper, J Burns, J Foulstone, E Pignatelli, M Zaina, S Hassan, A |
| author_sort | Harper, J |
| collection | OXFORD |
| description | The potent growth-promoting activity of insulin-like growth factor-II (IGF-II) is highly regulated during development but frequently up-regulated in tumors. Increased expression of the normally monoallelic (paternally expressed) mouse (Igf2) and human (IGF2) genes modify progression of intestinal adenoma in the Apc(Min/+) mouse and correlate with a high relative risk of human colorectal cancer susceptibility, respectively. We examined the functional consequence of Igf2 allelic dosage (null, monoallelic, and biallelic) on intestinal adenoma development in the Apc(Min/+) by breeding with mice with either disruption of Igf2 paternal allele or H19 maternal allele and used these models to evaluate an IGF-II-specific therapeutic intervention. Increased allelic Igf2 expression led to elongation of intestinal crypts, increased adenoma growth independent of systemic growth, and increased adenoma nuclear beta-catenin staining. By introducing a transgene expressing a soluble form of the full-length IGF-II/mannose 6-phosphate receptor (sIGF2R) in the intestine, which acts as a specific inhibitor of IGF-II ligand bioavailability (ligand trap), we show rescue of the Igf2-dependent intestinal and adenoma phenotype. This evidence shows the functional potency of allelic dosage of an epigenetically regulated gene in cancer and supports the application of an IGF-II ligand-specific therapeutic intervention in colorectal cancer. |
| first_indexed | 2024-03-07T02:21:13Z |
| format | Journal article |
| id | oxford-uuid:a3fa9b4f-3fd4-42ac-a8c6-0834a70f7f5c |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T02:21:13Z |
| publishDate | 2006 |
| record_format | dspace |
| spelling | oxford-uuid:a3fa9b4f-3fd4-42ac-a8c6-0834a70f7f5c2022-03-27T02:30:49ZSoluble IGF2 receptor rescues Apc(Min/+) intestinal adenoma progression induced by Igf2 loss of imprinting.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:a3fa9b4f-3fd4-42ac-a8c6-0834a70f7f5cEnglishSymplectic Elements at Oxford2006Harper, JBurns, JFoulstone, EPignatelli, MZaina, SHassan, AThe potent growth-promoting activity of insulin-like growth factor-II (IGF-II) is highly regulated during development but frequently up-regulated in tumors. Increased expression of the normally monoallelic (paternally expressed) mouse (Igf2) and human (IGF2) genes modify progression of intestinal adenoma in the Apc(Min/+) mouse and correlate with a high relative risk of human colorectal cancer susceptibility, respectively. We examined the functional consequence of Igf2 allelic dosage (null, monoallelic, and biallelic) on intestinal adenoma development in the Apc(Min/+) by breeding with mice with either disruption of Igf2 paternal allele or H19 maternal allele and used these models to evaluate an IGF-II-specific therapeutic intervention. Increased allelic Igf2 expression led to elongation of intestinal crypts, increased adenoma growth independent of systemic growth, and increased adenoma nuclear beta-catenin staining. By introducing a transgene expressing a soluble form of the full-length IGF-II/mannose 6-phosphate receptor (sIGF2R) in the intestine, which acts as a specific inhibitor of IGF-II ligand bioavailability (ligand trap), we show rescue of the Igf2-dependent intestinal and adenoma phenotype. This evidence shows the functional potency of allelic dosage of an epigenetically regulated gene in cancer and supports the application of an IGF-II ligand-specific therapeutic intervention in colorectal cancer. |
| spellingShingle | Harper, J Burns, J Foulstone, E Pignatelli, M Zaina, S Hassan, A Soluble IGF2 receptor rescues Apc(Min/+) intestinal adenoma progression induced by Igf2 loss of imprinting. |
| title | Soluble IGF2 receptor rescues Apc(Min/+) intestinal adenoma progression induced by Igf2 loss of imprinting. |
| title_full | Soluble IGF2 receptor rescues Apc(Min/+) intestinal adenoma progression induced by Igf2 loss of imprinting. |
| title_fullStr | Soluble IGF2 receptor rescues Apc(Min/+) intestinal adenoma progression induced by Igf2 loss of imprinting. |
| title_full_unstemmed | Soluble IGF2 receptor rescues Apc(Min/+) intestinal adenoma progression induced by Igf2 loss of imprinting. |
| title_short | Soluble IGF2 receptor rescues Apc(Min/+) intestinal adenoma progression induced by Igf2 loss of imprinting. |
| title_sort | soluble igf2 receptor rescues apc min intestinal adenoma progression induced by igf2 loss of imprinting |
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