A common thread interwoven throughout the literature of cancer biology is a wide-ranging abnormality of gene regulation, manifested by misprogramming of protein synthesis. This phenomenon encompasses virtually every means of identification of proteins, including antigens, hormones, growth factors, membrane components, and enzymes. Studies by the author and others of the activities of enzymes existing in multiple forms (termed isozymes) in a series of rat hepatomas ranging widely in growth rate, degree of differentiation, and other phenotypic properties has extended this concept and added to it a dimension of functional significance. Isozymes that are in high activity in adult liver and that are geared kinetically to catalyze specific hepatic functions are lost in varying degrees and generally depend on the growth rate and degree of differentiation. In fast growing, poorly differentiated hepatomas, these are replaced by high activities of isozymes that are normally low or absent in adult liver. In many instances, the isozymes that are expressed in poorly differentiated hepatomas are present also in fetal liver, thus pointing to reactivation of genes that were active in the fetus but were inactivated during normal embryonic development. The loss of isozymes that are under rigid host endocrine control, as well as other proteins that maintain the differentiated state, and the re-activation of genes coding for fetal or ectopic proteins are probably crucial factors in the initiation and maintenance of cellular proliferation.
Cancer 45:2975-2980, 1980.
EMBERS A N D GUESTS, I am grateful for the honor M conferred on me by the Society of Surgical
Oncology. I am happy to accept this award on behalf of the many people-students, co-workers, and colleagues who have contributed so much in both intellectual input and hard work. 1 am gratified also that by making this award your members, who are the frontline soldiers contending every day with this devastating human problem, recognize the contribution of those who are grappling with this problem in the laboratory.
1 also have to confess to some mixed feelings. Somehow awards for cancer research seem out of place considering how little we have accomplished, and how much more we still need to know before cancer can be brought under control. This is not undue modesty on my part; as the saying goes, cancer researchers have a great deal to be modest about.