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Increased expression of c‐ jun, but not retinoic acid receptor β, is associated with F9 teratocarcinoma stem cell differentiation induced by polyamine depletion
Author(s) -
Bjersing Jan L.,
Brorsson Astrid,
Heby Olle
Publication year - 1997
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/(sici)1097-4644(19971201)67:3<378::aid-jcb9>3.0.co;2-t
Subject(s) - retinoic acid , cellular differentiation , biology , endoderm , teratocarcinoma , retinoic acid receptor , microbiology and biotechnology , ornithine decarboxylase , messenger rna , cell culture , biochemistry , enzyme , gene , genetics
α‐Difluoromethylornithine (DFMO), an enzyme‐activated irreversible inhibitor of ornithine decarboxylase, and all‐ trans‐ retinoic acid (RA) are known to induce F9 teratocarcinoma stem cell differentiation. Both compounds induce the formation of the same cell type, i.e., parietal endoderm‐like cells expressing tissue plasminogen activator and collagen type IV α‐1. The present study shows that DFMO and RA induce terminal differentiation of F9 cells through different pathways. Thus, retinoic acid receptor (RAR) α mRNA is weakly expressed during DFMO treatment, but strongly induced during an early phase of RA treatment. RAR β mRNA is not detectable in DFMO‐treated cells, but very strongly induced by RA and maintained at a high level throughout the differentiative process. RAR γ mRNA is relatively strongly expressed in untreated control cells and remains at approximately the same level during DFMO‐induced differentiation. In RA‐treated cells, however, RAR γ mRNA is rapidly down‐regulated and becomes nondetectable during the final course of differentiation. These experiments show that the differentiation of F9 cells into parietal endoderm‐like cells does not necessarily involve changes in any of the RAR mRNA subtypes. Even though the steady‐state levels of the RAR α and RAR γ transcripts may be sufficient to support the differentiative process, our data clearly show that induction of RAR β mRNA transcription is neither a prerequisite for F9 cell differentiation, nor an absolute consequence of the elevated c‐ jun mRNA expression that is consistently observed during the course of parietal endoderm differentiation. J. Cell. Biochem. 67:378–385, 1997. © 1997 Wiley‐Liss, Inc.