Impaired transforming growth factor beta signalling in Barrett's carcinogenesis due to frequent SMAD4 inactivation.

ABSTRACT:

Background and aims

Transforming growth factor beta (TGF-beta) is frequently involved in gastrointestinal carcinogenesis although its contribution to oesophageal adenocarcinoma (AC) and its precursor Barrett's oesophageal epithelium (BE) metaplasia are unclear.

Methods

Expression of TGF-beta signalling components was assessed by reverse transcription-polymerase chain reaction (PCR), western blot, and immunohistochemistry in oesophageal endoscopic biopsies and cell lines. Genomic alterations in SMAD4 were characterised by fluorescence in situ hybridisation, methylation specific PCR, and sequencing. Functional integrity of TGF-beta signalling was assessed by characterisation of p21 and proliferation status. Smad4 negative BIC-1 cells were transiently transfected with smad4 and

SUBMITTER: Onwuegbusi BA 

PROVIDER: S-EPMC1856235 | biostudies-literature | 2006 Jun

REPOSITORIES: biostudies-literature