SUPPRESSION OF TUMORIGENICITY IN HUMAN TERATOCARCINOMA CELL-LINE PA-1BY INTRODUCTION OF CHROMOSOME-4

Teratocarcinomas are tumors that develop spontaneously in the gonads a nd usually contain a rapidly dividing, undifferentiated stem cell popu lation. Immature ovarian teratocarcinomas are highly malignant with on ly 30-60% of patients surviving for 2 years after diagnosis. We have u sed microcell fusion to introduce individually tagged normal human chr omosomes into the PA-1 human teratocarcinoma cell line. Introduction o f human chromosome 4 caused a change of cell morphology in culture and suppressed PA-1 tumorigenicity in nude mice, whereas addition of port ions of either chromosome 7 or 12 had no effect on the cell phenotype. The PA-1 cell line regained its tumorigenicity when the tagged chromo some 4 was lost under negative selection. We conclude that there is a putative tumor suppressor gene on human chromosome 4 whose expression interferes with the tumorigenicity of PA-1 cells.