The long-range objective is to understand enough about the factors that control mammalian cell growth to be able to apply this knowledge to the control of malignant growth. As a result of recent work, a broad picture is now available of the growth control of mammalian cells. Application of this knowledge requires additional information and experimentation. For example, detailed information is needed of the specific factors that control the growth of the epithelial cells that are most important in the origin of malignant tumors, in order to design rational procedures to control these tumors. Among other things, it is important to know whether growth inhibitors such as a growth inhibitor produced by kidney epithelial cells, can be used to restrict tumor growth. The kidney epithelial cell growth inhibitor is active on certain lung and mammary cells in culture. With CCL64 mink lung cells, for example, 60% inhibition of [?3?H]thymidine incorporation is observed at a 0.1-nanogram/ml concentration of the growth inhibitor. Injection of the growth inhibitor in vivo into human mammary carcinomas growing in nude mice inhibits [?3?H]thymidine incorporation into the tumors. Recently, this kidney epithelial cell growth inhibitor has been found to be very similar to, or identical with, transforming growth factor beta. Each of these substances is active in the assays used for the other, and their general properties are identical. These results indicate that the same substance can be either an extremely active growth stimulator or an extremely active growth inhibitor, depending on the cells and assay conditions. The relevance of this in vivo and an understanding of the in vivo role of this growth inhibitor/transforming growth factor beta will be of major interest. (J)
| Hanks, S K; Armour, R; Baldwin, J H et al. (1988) Amino acid sequence of the BSC-1 cell growth inhibitor (polyergin) deduced from the nucleotide sequence of the cDNA. Proc Natl Acad Sci U S A 85:79-82 |
| Brown, K D; Holley, R W (1987) Insulin-like synergistic stimulation of DNA synthesis in Swiss 3T3 cells by the BSC-1 cell-derived growth inhibitor related to transforming growth factor type beta. Proc Natl Acad Sci U S A 84:3743-7 |
| Holley, R W; Baldwin, J H; Greenfield, S (1987) Isolation of the BSC-1 monkey kidney cell growth inhibitor. Methods Enzymol 146:163-7 |
| Holley, R W; Baldwin, J H; Greenfield, S et al. (1985) A growth regulatory factor that can both inhibit and stimulate growth. Ciba Found Symp 116:241-52 |
| Fine, L G; Holley, R W; Nasri, H et al. (1985) BSC-1 growth inhibitor transforms a mitogenic stimulus into a hypertrophic stimulus for renal proximal tubular cells: relationship to Na+/H+ antiport activity. Proc Natl Acad Sci U S A 82:6163-6 |
