PROLACTIN (PRL)-DEPENDENT EXPRESSION OF A ZINC-FINGER PROTEIN-ENCODING GENE, GFI-1, IN NB2 LYMPHOMA-CELLS - CONSTITUTIVE EXPRESSION IN AUTONOMOUS SUBLINES

The proliferation of cultured rat Nb2 lymphoma cells is dependent on p rolactin (PRL) acting as the principal growth factor. Previously, PRL- independent Nb2 sublines were obtained by PRL starvation of the parent line and cloning of surviving cells. Development of PRL independence was in some cases found to be associated with a reciprocal translocati on involving chromosome 14 at breakpoint 14p22. In the present study, a novel, 14p22 zinc finger protein-encoding gene, Gfi-1, has been exam ined for a role in Nb2 cell proliferation. PRL-dependent Nb2 cells exp ressed the gene during active growth; in comparison, in stationary, ea rly G1-arrested cells obtained by an 18 hr lactogen starvation, Gfi-1 gene expression was markedly decreased. Addition of PRL to such statio nary cells led to induction of Gfi-1 gene expression within a few hr w ith a maximum in late G1. Actively growing cells from 5 different PRL- independent Nb2 sublines, cultured in chemically defined, mitogen-free medium, expressed the gene constitutively. In two sublines, carrying the 14p22 rearrangement, the gene was markedly overexpressed. The resu lts suggest the Gfi-1 gene product has a regulatory role in Nb2 cell m itogenesis and that unscheduled activation could contribute to loss of PRL dependency.