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)|
|Number of pages||6|
|State||Published - Nov 1 1998|
ASJC Scopus subject areas
- Cancer Research