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Suppression of Tumorigenicity in Human Teratocarcinoma Cell Line PA-1 by Introduction of Chromosome 4¹

Department of Biochemistry, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, K1H 8M5 Canada [I. J. M-J., M. D. S., M. C.], and Environmental Health Centre, Tunney's Pasture, Ottawa, Ontario, K1A 0L2 Canada [D. B.]

Teratocarcinomas are tumors that develop spontaneously in the gonads and usually contain a rapidly dividing, undifferentiated stem cell population. Immature ovarian teratocarcinomas are highly malignant with only 30–60% of patients surviving for 2 years after diagnosis. We have used microcell fusion to introduce individually tagged normal human chromosomes into the PA-1 human teratocarcinoma cell line. Introduction of human chromosome 4 caused a change of cell morphology in culture and suppressed PA-1 tumorigenicity in nude mice, whereas addition of portions of either chromosome 7 or 12 had no effect on the cell phenotype. The PA-1 cell line regained its tumorigenicity when the tagged chromosome 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.

¹ This project was supported by a grant from the Cancer Research Society, Montréal, PQ, Canada. I. J. M-J. and M. D. S. are recipients of Ontario Graduate Scholarships.

² To whom correspondence should be addressed.

Received 1/20/94. Accepted 4/ 5/94.

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