Transforming growth factor beta(1) selectively ...
|Title||Transforming growth factor beta(1) selectively regulates ferritin gene expression in malignant H-ras-transformed fibrosarcoma cell lines|
|Author(s)||J. Lo, Robert A. R. Hurta|
|Journal||Biochemistry and Cell Biology / Biochimie Et Biologie Cellulaire|
|Abstract||Transforming growth factor beta(1) is an important growth regulator in many cell types, usually exerting a negative effect on cellular growth. Inhibition of DNA synthesis and cell proliferation is frequently lost during malignant transformation, and in some cases, tumor cell proliferation is actually stimulated by TGF-beta(1). The present study demonstrates a novel link between alterations in TGF-beta(1), regulation during malignant conversion, and the expression of ferritin, an important activity involved in a number of biological functions including iron homeostasis and cell-growth control. A series of H-ras-transformed mouse 10 T 1/2 cell lines, exhibiting increasing malignant potential, was investigated for possible TGF-beta(1)-mediated changes in ferritin gene expression. Selective induction of gene expression was observed, since only H-ras-transformed cells with malignant potential exhibited marked elevations in ferritin gene expression, in particular, alterations in H-ferritin gene expression. The regulation of H-ferritin gene expression in response to TGF-beta(1) did not involve alterations in transcription, but occurred through mechanisms of post-transcriptional stabilization of the H-ferritin mRNA. Additionally, evidence was obtained for a cycloheximide-sensitive regulator of H-ferritin gene expression, since the presence of this protein synthesis inhibitor increased H-ferritin message levels, and in combination with TGF-beta(1), cooperated in an additive manner to augment H-ferritin gene expression. These results show for the first time that TGF-beta(1) can regulate ferritin gene expression in malignant H-ras transformed cells, and suggest a mechanism for growth factor stimulation of malignant cells, in which early alterations in the control of H-ferritin gene expression are important.|
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