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| Transforming growth factor beta type I receptor kinase mutant associated with metastatic breast cancer |
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| Author(s): Chen TP, Carter D, Garrigue-Antar L, Reiss M |
| Source: CANCER RESEARCH Volume: 58 Issue: 21 Pages: 4805-4810 Published: NOV 1 1998 |
| Times Cited: 94 References: 47 |
| Abstract: Malignant breast carcinoma cell lines are frequently refractory to transforming growth factor beta (TGF-beta)-mediated cell cycle arrest. To identify molecular mechanisms of TGF-beta resistance, we have conducted a comprehensive structural analysis of the TGF-beta receptor types I (T beta R-I) and II (T beta R-II) genes in primary human breast carcinomas and associated axillary lymph node metastases. No evidence for loss of expression (n = 14) or structural alterations of the T beta R-II gene (n = 30) were identified. However, 2 of 31 primary carcinomas and 5 of 12 lymph node metastases carried a C to A transversion mutation resulting in a serine to tyrosine substitution at codon 387 (S387Y) of the T beta R-I receptor gene. This T beta R-I mutant has a diminished ability to mediate TGF-beta-dependent effects on gene expression as compared with wild-type T beta R-I.S387Y is the first reported mutation in the T beta R-I gene in human cancer that was primarily associated with lymph node metastases in the present series. |
| Document Type: Article |
| Language: English |
| Reprint Address: Reiss, M (reprint author), Yale Univ, Sch Med, Dept Internal Med, Sect Med Oncol, 333 Cedar St,NS291, New Haven, CT 06520 USA |
Addresses:
1. Yale Univ, Sch Med, Yale Canc Ctr, Dept Med, New Haven, CT 06520 USA
2. Yale Univ, Sch Med, Yale Canc Ctr, Dept Pathol, New Haven, CT 06520 USA |
| Publisher: AMER ASSOC CANCER RESEARCH, PO BOX 11806, BIRMINGHAM, AL 35202 USA |
| Subject Category: Oncology |
| IDS Number: 134XE |
| ISSN: 0008-5472 |
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