© 1994 Oxford University Press
research-article |
Growth suppression of transformed BALB/c 3T3 cells by transforming growth factor ß1 occurs only in the presence of their normal counterparts
Unit of Multistage Carcrnogenesis, International Agency for Research on Cancer 150 crairs Albert Thanas, 691372 Lyon cedex 08, France
1 Present address: Laboratory of Molecular Carcinogenesis, National Institute of Envirorunental Health Sciences, Research Triangle Park, NC 27709, USA
2To whom all correspondence can be addressed
Transforming growth factor ß1 (TGF-ß1) enhances the yield of transformed foci of BALB/c 3T3 cells, but the continuous presence of TGF-ß1 after foci formation inhibits the growth of transformed foci. The focus-forming ability of Ha-ras-, v-src-and PyMT-transformed cells growing on a monolayer of non-transformed cells was completely suppressed by TGF ß1, whereas growth of the transformed cells was little inhibited by TGF-ß1 in the absence of their normal counterparts. The inhibition by TGF-ß1 of focus formation by transformed BALB/c 3T3 cells on a normal cell monolayer remained when TGF-ß1 was removed from the culture medium after 2 weeks. However, the transformed cells were not killed, since they grew in culture conditions under which only transformed cells are able to grow (soft agar). These results suggest that TGF-ß1 suppresses growth of transformed cells in the presence of normal cells. Furthermore, when non-transformed cells were treated with TGF-ß1 before co-culture with Ha-ras-transformed cells, formation of transformed foci was inhibited. When normal and transformed cells were cultured in the same dish but separated physically, focus formation was still Inhibited. On the other hand, TGF-ß1 enhanced the growth and changed the morphology of non-transformed cells only in the presence of transformed counterparts. The growth inhibitory effect of TGF-ß1 on transformed cells and its growth stlmulatory effect on non-transformed cells in co-culture conditions suggest the induction of reciprocal paracrine growth regulatory factors. As TGF-ß1 inhibits the growth of transformed BALB/c 3T3 cells only in the presence of their normal counterparts, a paracrine negative growth control mechanism appears to be operating.