T transversion in exon 3 of TbetaR-II that introduces a premature stop codon (E142Stop) and presumably results in the synthesis of a truncated soluble exoreceptor. In one tumor, a silent A-->C transversion mutation that may affect mRNA splicing was present in exon 6 of TbetaR-I. In addition, 7 of 16 cases were heterozygous for a G-->A polymorphism in intron 7 of TbetaR-I. Finally, we identified a 9 base pair in-frame germline deletion in exon 1 of TbetaR-I resulting in loss of 3 of 9 sequential alanine residues at the N-terminus in 6 of 16 cases. Analysis of specimens from case-control studies indicated that carriers of this del(GGC)3 TbetaR-I variant allele may be at a increased risk for the development of cervical carcinoma (p=0.22). Furthermore, the response of cells expressing the variant receptor to TGFbeta was diminished. Our results support the notion that diverse alterations in the TGFbeta signaling pathway may play a role in the development of cervical cancer.
| Grant Information: |
CA41556 United States CA NCI NIH HHS |
| Substance Nomenclature: |
0 (Receptors, Transforming Growth Factor beta) |
| Entry Date(s): |
Date Created: 19990609 Date Completed: 19990617 Latest Revision: 20221207 |
| Update Code: |
20231215 |
| DOI: |
10.1002/(sici)1097-0215(19990702)82:1<43::aid-ijc9>3.0.co;2-0 |
| PMID: |
10360819 |
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| Autor: |
Chen T; Section of Medical Oncology and Yale Cancer Center, Yale University School of Medicine, New Haven, CT 06520-8032, USA., de Vries EG, Hollema H, Yegen HA, Vellucci VF, Strickler HD, Hildesheim A, Reiss M |
| Jazyk: |
angličtina |
| Zdroj: |
International journal of cancer [Int J Cancer] 1999 Jul 02; Vol. 82 (1), pp. 43-51. |
| DOI: |
10.1002/(sici)1097-0215(19990702)82:1<43::aid-ijc9>3.0.co;2-0 |
| Abstrakt: |
The development and progression of invasive uterine cervical carcinomas appear to be associated with the progressive loss of sensitivity to transforming growth factor-beta (TGFbeta)-mediated cell cycle arrest. In order to identify possible molecular mechanisms responsible for TGFbeta resistance, we screened the 7 exons of the type II (TbetaR-II) TGFbeta receptor and the 9 exons of the type I (TbetaR-I) TGFbeta receptor genes for mutations in 16 paraffin-embedded primary invasive cervical carcinoma specimens. In one of these carcinomas, we found a novel G-->T transversion in exon 3 of TbetaR-II that introduces a premature stop codon (E142Stop) and presumably results in the synthesis of a truncated soluble exoreceptor. In one tumor, a silent A-->C transversion mutation that may affect mRNA splicing was present in exon 6 of TbetaR-I. In addition, 7 of 16 cases were heterozygous for a G-->A polymorphism in intron 7 of TbetaR-I. Finally, we identified a 9 base pair in-frame germline deletion in exon 1 of TbetaR-I resulting in loss of 3 of 9 sequential alanine residues at the N-terminus in 6 of 16 cases. Analysis of specimens from case-control studies indicated that carriers of this del(GGC)3 TbetaR-I variant allele may be at a increased risk for the development of cervical carcinoma (p=0.22). Furthermore, the response of cells expressing the variant receptor to TGFbeta was diminished. Our results support the notion that diverse alterations in the TGFbeta signaling pathway may play a role in the development of cervical cancer. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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