A. Isolation of hormone regulated genes in the human MCF-7 breast cancer cell line. The purpose of this project is to clone, sequence, and identify genes which are important in the estrogen induction of the tumorigenic phenotype in MCF-7 human breast cancer cells. We have constructed a cDNA library from estrogen treated human breast cancer cells and have isolated from the library several cDNA clones which are regulated by estrogen treatment of the cells. Several of the clones represent genes whose transcription is stimulated shortly after exposure of the cells to estrogen. Estrogen treatment for approximately 24 hr results in growth stimulation in vitro and the continuous presence of estrogen required for tumor formation in the nude mouse. It is our goal to characterize the genes we have cloned and study their relevance to the tumorigenic phenotype. We have also isolated the gene whose expression is inhibited by estrogen treatment of the cells. Moreover, antiestrogens, which reversibly stops cell growth, causes the expression of this gene to be enhanced. Since this phenomenon does not result from mere arrest of cell growth but seems to be hormonal dependent, we are actively investigating the hypothesis that antiestrogens may operate through induced genes which are inhibitory to cell growth. We are also asking the question if the clone we have isolated represents the gene for one of these growth inhibitory factors. B. Molecular cloning of human fibroblast growth factor. The purpose of this project to isolate a full length cDNA clone of the growth stimulatory protein known as fibroblast growth factor. FGF is a protein produced by certain human carcinoma cells including the human breast cancer cell.
