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 prolactin (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 translocation involving chromosome 14 at breakpoint 14p22. In the present study, a novel, 14p22 zinc finger protein-encoding gene, Gfi-1, has been examined for a role in Nb2 cell proliferation. PRL-dependent Nb2 cells expressed the gene during active growth; in comparison, in stationary, early G1-arrested cells obtained by an 18 hr lactogen starvation, Gfi-1 gene expression was markedly decreased. Addition of PRL to such stationary cells led to induction of Gfi-1 gene expression within a few hr with 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 results suggest the Gfi-1 gene product has a regulatory role in Nb2 cell mitogenesis and that unscheduled activation could contribute to loss of PRL dependency.
Gilks
C B
CB
Department of Pathology, University of British Columbia, Vancouver, Canada.
Porter
S D
SD
Barker
C
C
Tsichlis
P N
PN
Gout
P W
PW
D000818:Animals; D015139:Blotting, Southern; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000235:genetics*; D015870:Gene Expression / Q000187:drug effects*; D008223:Lymphoma / Q000378:metabolism* / Q000473:pathology; D011388:Prolactin / Q000494:pharmacology*; D051381:Rats; D014157:Transcription Factors; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured; D016335:Zinc Fingers / Q000235:genetics*
D004268:DNA-Binding Proteins; C498276:Gfi1 protein, rat; D014157:Transcription Factors; D011388:Prolactin; D004247:DNA