All cells studied to date require transferrin for growth. We and others have shown that antibodies to the transferrin receptor block the growth of lymphoblastoid cell lines. In mitogen- stimulated lymphocytes, these antibodies block proliferation. We are studying the processes which regulate the appearance of these receptors in lymphocytes and lymphoblastoid cell lines, and the function of these receptors in cell growth and metabolism. We have demonstrated that G1 arrest occurs in both normal and malignant cells when transferrin receptors are blocked, even if cells are expressing high levels of growth factor receptor messenger RNA and c-myc and c-myb messenger RNA. Furthermore, either blockage of calcium channels or addition of cAMP to cells results in G1 arrest and loss of transferrin receptor mRNA. The effect of cAMP can be detected at the level of transcription. We have begun to study the role of nuclear proteins in the transition of T cells from G0 to S phase. In an initial study, a c- myc antisense oligomer completely blocked the appearance of c- myc protein in mitogen treated T cells, yet these cells went on to express IL-2 receptors, transferrin receptors and DNA polymerase alpha protein. Yet they failed to synthesize DNA. We plan to continue to use antisense constructs to various nuclear proteins to study their role(s) in cell growth and activation. Initially, we are examining the requirements for several nuclear proteins in DNA polymerase alpha activity. To date, we have determine that two such proteins, c-myc and Ki-67, are required for polymerase alpha activity in vitro.
