Open AccessThe mitogen-regulated protein/proliferin transcript is degraded in primary mouse embryo fibroblast but not 3T3 nuclei: altered RNA processing correlates with immortalization.
Author(s) -
Uriel M. Malyankar,
Susan R. Rittling,
Allison Connor,
David T. Denhardt
Publication year - 1994
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.91.1.335
Subject(s) - biology , microbiology and biotechnology , 3t3 cells , messenger rna , blot , gene expression , northern blot , rna , embryo , immortalised cell line , fibroblast , cell culture , gene , genetics , transfection
An understanding of what changes occur in the control of gene expression when mammalian cells "spontaneously" immortalize is important to our knowledge of how cancer develops. We describe here an alteration in 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 derived from the MEFs. Incompletely processed nuclear transcripts of the mitogen-regulated protein/proliferin gene can be detected in MEF RNA preparations by northern blotting and reverse transcriptase polymerase chain reaction analyses, although at roughly half the abundance observed in 3T3 cells. We hypothesize that some attribute of the primary unprocessed transcript determines its assignment to this unique degradative pathway. These results reveal that during passage of MEFs according to a 3T3 regimen the ability of the primary cells to suppress the expression of certain genes by degrading the nuclear transcript is lost concomitantly with immortalization.