Transforming growth factor β type I receptor kinase mutant associated with metastatic breast cancer

Taiping Chen, Darryl Carter, Laure Garrigue-Antar, Michael Reiss

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)4805-4810
Number of pages6
JournalCancer Research
Volume58
Issue number21
StatePublished - Nov 1 1998
Externally publishedYes

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Chen, T., Carter, D., Garrigue-Antar, L., & Reiss, M. (1998). Transforming growth factor β type I receptor kinase mutant associated with metastatic breast cancer. Cancer Research, 58(21), 4805-4810.