Altered responsiveness of rat liver epithelial cells to transforming growth factor beta 1 following their transformation with v-raf.
The effects of transforming growth factor beta (type 1) (TGF-beta 1) on DNA synthesis, cell proliferation, and protein synthesis were examined in a series of v-raf-transformed rat liver epithelial (RLE) cells, which exhibit a range of transformed phenotypes. All of the transformed cells were relatively resistant to the growth-inhibitory effects of TGF-beta 1, compared to normal RLE cells and control cells infected with a helper virus. The more tumorigenic cell lines had very few surface receptors for TGF-beta 1 and showed no increase in the secretion of a number of specific proteins, including fibronectin, following TGF-beta 1 treatment. In contrast, the more normal-looking, less tumorigenic v-raf-transformed cells bound similar amounts of TGF-beta 1 as normal RLE and control cells and showed a similar pattern of TGF-beta 1-stimulated protein secretion. These findings suggest that the effects of TGF-beta 1 on cell proliferation and on the expression of certain secreted proteins are mediated through different mechanisms. Following transformation of RLE cells with v-raf, the signalling pathways controlling TGF-beta 1 growth inhibition are perturbed, while those involved in regulating the synthesis of certain proteins may remain intact. Thus, the escape from the various distinct biological effects of TGF-beta 1 may be an important stage in the progression of neoplastic transformation of RLE cells in vitro.
Huggett
A C
AC
Laboratory of Experimental Carcinogenesis, National Cancer Institute, NIH, Bethesda, Maryland 20892.
Hampton
L L
LL
Ford
C P
CP
Wirth
P J
PJ
Thorgeirsson
S S
SS
D000818:Animals; D015152:Blotting, Northern; D002455:Cell Division / Q000187:drug effects; D002471:Cell Transformation, Neoplastic; D004247:DNA / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D015180:Electrophoresis, Gel, Two-Dimensional; D004848:Epithelium / Q000187:drug effects; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis / Q000187:drug effects; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta; D014170:Transformation, Genetic; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000378:metabolism / Q000494:pharmacology*
D016326:Extracellular Matrix Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D004247:DNA