THE MITOGEN-REGULATED PROTEIN PROLIFERIN TRANSCRIPT IS DEGRADED IN PRIMARY MOUSE EMBRYO FIBROBLAST BUT NOT 3T3 NUCLEI - ALTERED RNA PROCESSING CORRELATES WITH IMMORTALIZATION

An understanding of what changes occur in the control of gene expressi on when mammalian cells ''spontaneously'' immortalize is important to our knowledge of how cancer develops. We describe here an alteration i n regulation that occurs when primary mouse embryo fibroblasts (MEFs) are immortalized according to a 3T3 regimen. Mitogen-regulated protein /proliferin mRNA is undetectable in northern blots of RNA from (mortal ) MEFs, whereas it is readily detected in immortal 3T3 cell lines deri ved from the MEFs. Incompletely processed nuclear transcripts of the m itogen-regulated protein/proliferin gene can be detected in MEF RNA pr eparations by northern blotting and reverse transcriptase polymerase c hain reaction analyses, although at roughly half the abundance observe d in 3T3 cells. We hypothesize that some attribute of the primary unpr ocessed transcript determines its assignment to this unique degradativ e pathway. These results reveal that during passage of MEFs according to a 3T3 regimen the ability of the primary cells to suppress the expr ession of certain genes by degrading the nuclear transcript is lost co ncomitantly with immortalization.