Heterogeneity in the transforming growth factor beta response of esophageal cancer cells.
The role of the transforming growth factor beta (TGFbeta) pathway in the development and progression of esophageal cancers is poorly understood. As an initial step in clarification of this issue, the functional status of the TGFbeta pathway was evaluated in a panel of esophageal cancer derived cell lines. Both adenocarcinoma and squamous cell carcinoma derived lines were represented. Although the TGFbeta pathway was intact and functional in four of the five cell lines, only one of them was growth inhibited by TGFbeta. In one cell line, the loss of a growth inhibitory response to TGFbeta could be explained by decreased expression of Smad 4 and a general inability to activate TGFbeta responsive promoters. In the other three cell lines, TGFbeta was able to activate transcription of TGFbeta responsive promoters, but unable to downregulate transcription of c-myc. Taken together these findings indicate that a selective loss in the ability of TGFbeta to regulate expression of a key component of the growth inhibitory pathway may contribute to the poor prognosis of esophageal cancers.
Lebman
Deborah A
DA
Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond 23298-0678, USA. dlebman@hsc.vcu.edu
Edmiston
Jeffery S
JS
Chung
Theodore D
TD
Snyder
Steven R
SR
D015536:Down-Regulation; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016259:Genes, myc; D006801:Humans; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D016212:Transforming Growth Factor beta