Journal
JOURNAL OF PATHOLOGY
Volume 205, Issue 1, Pages 14-20Publisher
WILEY
DOI: 10.1002/path.1683
Keywords
human keratinocytes; transforming growth factor-beta; cancer; regression
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We have shown previously that transforming growth factor-beta (TGF-beta) is a potent tumour suppressor in Smad4-deficient human malignant oral keratinocytes but the mechanism by which this occurs is unknown. In the present study, we show that over-expression of TGF-beta1 causes regression of tumours derived from Smad4-deficient oral keratinocytes transplanted orthotopically to athymic mice. Further, tumour regression is associated with the induction of apoptosis without changes in cell proliferation. In vitro, TGF-beta1 I did not induce apoptosis directly in these cells but sensitized cells to cisplatin, but not Fas, -induced cell death. The data suggest that TGF-beta1 induces tumour regression in vivo by Smad4-independent pathways that sensitize keratinocytes to mitochondrial-mediated apoptosis. Copyright (D 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley Sons, Ltd.
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