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The Reversible Expression of an Adult Isozyme Locus, Gdc-1, in Tumors of the Mouse¹

The Jackson Laboratory,² Bar Harbor, Maine 04609

Tumors of the mouse possess 2 isozymic forms of L-glycerol-3-phosphate dehydrogenase (-GPDH) (EC 1.1.1.8) that can be distinguished from each other by their heat inactivation and electrophoretic properties. These isozymes share certain structural features, since dissociation and reassociation of mixtures of the 2 isozymes lead to the generation of a hybrid molecular species. This finding suggests that the structural genes for these isozymes are closely related.

A number of spontaneous and transplantable tumors of the mouse have been analyzed in order to assess whether the pattern of embryonic and adult -GPDH isozyme expression is correlated with the degree of tumor differentiation. The results indicate that no correlation between the type of isozyme expressed and the degree of tumor differentiation or growth rate was evident. A striking correlation exists, however, between the physical form of the tumor and isozyme expression; all solid tumors possess, predominantly, the adult isozymic form of L-glycerol-3-phosphate dehydrogenase, whereas all ascites tumors, including embryoid bodies from ovarian and testicular teratomas, possess the embryonic form. A solid tumor, the C1300 neuroblastoma, that initially possessed the adult isozyme, was cultured in vitro; this resulted in the disappearance of the adult isozyme and predominant expression of the embryonic isozyme. Reinjection of cultured neuroblastoma cells into a host mouse produced a solid tumor that possessed the adult isozyme.

The exclusive presence of either adult -GPDH in solid tumor growths or embryonic -GPDH in ascites tumor growths after converting from one physical form of the tumor to the other, strongly supports a genetic regulatory mechanism which depends on the reversible repression and activation of the structural loci for these isozymes.

¹ This work is supported by USPHS Grants HD 08431 and HD 05523 from the National Institute of Child Health and Human Development and CA-05985 from the National Cancer Institute.

² The Jackson Laboratory is fully accredited by the American Association for Accreditation of Laboratory Animal Care.

Received 2/13/76. Accepted 6/29/76.