Abstract
Malignant breast carcinoma cell lines are frequently refractory to transforming growth factor β (TGF-β)-mediated cell cycle arrest. To identify molecular mechanisms of TGF-β resistance, we have conducted a comprehensive structural analysis of the TGF-β receptor types I (TβR-I) and II (TβR-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 TβR-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 TβR-I receptor gene. This TβR-I mutant has a diminished ability to mediate TGF-β-dependent effects on gene expression as compared with wild-type TβR-I. S387Y is the first reported mutation in the TβR-I gene in human cancer that was primarily associated with lymph node metastases in the present series.
Original language | English (US) |
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Pages (from-to) | 4805-4810 |
Number of pages | 6 |
Journal | Cancer Research |
Volume | 58 |
Issue number | 21 |
State | Published - Nov 1 1998 |
Externally published | Yes |
ASJC Scopus subject areas
- Cancer Research
- Oncology