In this study, we report the occurrence of missense mutations of the transforming growth factor β (TGFβ) type II receptor gene in two human squamous head and neck carcinoma cell lines. Both mutations are G:C→C:G transversions, which result in the replacement of a glutamic acid by a glutamine, and of an arginine by a proline residue, respectively. Moreover, both are located at highly conserved sites within the serine-threonine kinase domain. One of the mutants appears to be defective in its autophosphorylation as well as in the transphosphorylation of the TGFβ type I receptor protein, whereas the second mutant appears to be constitutively activated. These are the first reported naturally occurring nucleotide substitution mutations in the TβR-II gene in human head and neck cancer cells, which may explain their resistance to TGFβ1-mediated cell cycle arrest.
Supported in part by USPHS Award CA41556 (to M. R.) from the National Cancer Institute (including a Supplement for Underrepresented Minorities to Grant CA41556 from the National Cancer Institute to T. M. A.) and by a fellowship grant from the French Association pour la Recherche sur le Cancer (L. G-A.).