This research describes experiments that will result in a better understanding of the role growth factors play in malignant transformation. It is based upon the hypothesis that malignant transformation is at least a two-step process. One step is a cellular change in response to growth factors so that the cells respond by expressing traits common to tumor cells. The other step is the autocrine secretion of transforming growth factors. In this we will purify the transforming growth factors produced by a tumorigenic chemically transformed mouse salivary gland cell. The messenger RNAs and cellular genes for these growth factors will be obtained as molecular clones in bacterial plasmids. The biosynthesis of the growth factors by the tumor cells will be studied at the protein and nucleic acid level. We will also study why cells vary in their responsiveness to growth factor-induced growth in agar using a series of subclones of F2408 cells and normal fibroblasts. The experiments will involve establishing serum-free culture conditions of cells and studying their response to added growth factors and transforming viruses. (J)
