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Analysis of the differentiation‐promoting potential of inducible c‐fos genes introduced into embryonal carcinoma cells.
Author(s) -
Rüther U.,
Wagner E.F.,
Müller R.
Publication year - 1985
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1002/j.1460-2075.1985.tb03850.x
Subject(s) - biology , embryonal carcinoma , gene , carcinoma , cellular differentiation , cancer research , genetics , microbiology and biotechnology
To investigate the differentiation‐promoting potential of c‐fos in embryonal carcinoma cells (EC cells) we have designed various human metallothionein promoter‐mouse‐c‐fos gene constructs containing also the selectable SV40 promoter‐driven neo gene. Upon transfection into F9 EC cells and selection for neo resistance, the following results were obtained. (i) With each of the constructs, colonies of morphologically altered and differentiated (i.e., TROMA‐1 and TROMA‐3 expressing) cells were identified. (ii) Expression of c‐fos was required to affect the differentiation state of F9 cells to a significant extent, but a low level was sufficient; no enhancement of differentiation was noticeable even after 100‐fold induction of c‐fos expression by cadmium. (iii) F9 cell clones were isolated which, in spite of very high levels of exogenous c‐fos expression, had stem cell morphology. These cells, however, continuously generated morphologically altered and differentiated cells upon subculturing. (iv) In other EC cell lines, which resemble stem cells more closely than the ‘partially differentiated’ F9 cells, c‐fos expression showed either a less pronounced (P19 cells) or no differentiation‐promoting effect at all (PC13 cells). Our results suggest that the c‐fos gene product acts in concert with other, probably ‘spontaneously’ occurring events to promote differentiation of certain EC cell lines.