Carcinogenesis, Vol 18, 1867-1870, Copyright © 1997 by Oxford University Press
K Hattori, M Okamoto and R Oyasu
Transforming growth factor beta1 (TGFbeta1) is a potent growth inhibitor
for most cells, including neoplastic cells. However, there are several
types of malignant cells that are resistant to its growth- inhibitory
effect. LMC19, a highly malignant rat urothelial cell line, lacks TGFbeta1
receptor (TbetaRI) and is insensitive to the growth- suppresive effect of
TGFbeta1. We transfected an expression vector containing human TbetaRI into
this cell line. In control cells transfected with the neo gene alone, no
inhibitory effect on growth was observed in vitro by the addition of
anti-TGFbeta1 antibody or recombinant TGFbeta1 into serum-free medium. In
contrast, the growth of all transfectants tested was inhibited
significantly under serum-free conditions because of their endogenous
TGFbeta synthesis. The growth was reduced further by the addition of
recombinant TGFbeta1. This response pattern is consistent with TGFbeta1
mediating its effects by an autocrine and paracrine mechanism. The
tumorigenicity of the cells was tested in a heterotopically transplanted
urinary bladder system, which was generated as an orthotopic test site in
athymic nude mice. All nine mice tested receiving control cells formed
deeply invasive, undifferentiated-cell carcinomas and multiple metastatic
foci in the lungs. In contrast, none of the mice receiving transfectants of
TbetaRI formed bladder tumors or metastases. Taken together, these
observations indicate that TbetaRI exhibits a potent tumor suppressor
effect in bladder carcinoma.
ARTICLES
Transforming growth factor beta type I receptor acts as a potent tumor suppressor in rat bladder carcinoma
Department of Pathology, Northwestern University Medical School, Chicago, IL 60611, USA.
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