Centre de Neurochimie , CNRS , Strasbourg , France .
Oncogene 6 : 219-21 ( 1991)
Abstract
The expression of the proto-oncogenes c-fos , c-jun , jun B and jun D was monitored in quiescent C3H10T1/2 fibroblasts after stimulation with PDGF .
The mRNA level of c-fos , c-jun and jun B , but not of jun D , was stimulated by PDGF .
The inductions were abolished when genistein , a specific tyrosine protein kinase inhibitor , was added concomitantly with PDGF , a condition in which DNA synthesis is known to be inhibited .
As already shown previously , treatment with PDGF and genistein for 4h followed by the replacement with fresh medium induces the progression of the cells through the G1 phase of their growth-division cycle , without phospholipase C activation .
The removal of PDGF and genistein was accompanied by an important increase in c-fos , c-jun and jun B mRNA expression , which correlated with the entrance of cells into G1 phase .
Thus , the proto-oncogene expressions induced by PDGF are also obtained in the absence of phospholipase C activation .
This result also suggests that the mRNA levels of c-jun , jun B and to a lesser degree c-fos are positively regulated by tyrosine protein kinase activity , whereas jun D is negatively regulated .
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Hubrecht Laboratory , Netherlands Institute for Developmental Biology , Utrecht .
Dev Biol 142 : 406-13 ( 1990)
Abstract
Embryonic stem ( ES ) cells , derived in culture directly from the inner cells mass ( ICM ) of blastocysts , more closely resemble their embryonic counterparts than the more commonly used embryonal carcinoma ( EC ) cells derived from teratocarcinomas .
In view of the potential role of growth factors in early development , we have now followed changes in the expression of transforming growth factor beta ( in particular TGF beta 1 , beta 3 , beta 4 ) , platelet-derived growth factor ( PDGF-A , PDGF-B ) and insulin-like growth factor ( IGF II ) during the differentiation of ES cells in monolayer .
When maintained in medium conditioned by Buffalo rat liver cells ( BRL-CM ) to inhibit differentiation , ES cells expressed 2.5 and 1.8 kb transcripts for TGF beta 1 , as well as transcripts for TGF beta 4 , PDGF-A , and low levels of PDGF-B , but not TGF beta 3 or IGF II .
After formation of parietal endoderm-like cells by addition of retinoic acid ( RA ) to BRL-CM , the 1.8-kb transcript of TGF beta 1 and PDGF-A expression were reduced , IGF II mRNA and a single TGF beta 3 transcript of 3.8 kb were induced while PDGF-B and TGF beta 4 remained virtually unchanged .
By contrast , in ES cells induced to differentiate by the absence of BRL-CM , unusual transcripts for TGF beta 3 of 3.0 and 6.0 kb became detectable and PDGF-B expression increased .
The changes in growth factor expression in ES cells are compared with those in F9 and P19 EC cells induced to differentiate in monolayer by RA .