PI3-KINASE ACTIVITY IS NECESSARY FOR F9 TERATOCARCINOMA CELL PROLIFERATION
M. S. Liangouzova,1 I. A. Tchuikin, V. A. Pospelov
Institute of Cytology RAS, St. Petersburg, Russia;
1 e-mail:
malya@au.ru
Embryonic carcinoma (EC) cells and embryonic stem (ES) cells have short cell cycles and, accordingly,
proliferate very fast. Serum starvation does not suppress proliferation of EC and ES cells that allows to assume independence
of their proliferation from the activity of cascades induced by serum. In the present work, we used flow cytometry to investigate
how specific MAP-kinase and PI3-kinase inhibitors may influence proliferation and cell cycle of EC F9 cells. It is established that
inhibitors of ERK-, INK- and p38-kinases do not suppress EC F9 cell proliferation. It is possible to assume that proliferation of EC
cells is supported by constitutive activity of downstream cell cycle regulators, for example, E2F1 transcription factor.
Since PI3-kinase inhibitor LY294002 causes reduction of S-phase and accumulation of G1-phase F9 cells,
PI3-kinase mediated cascades seem to be constantly activated and involved in phosphorylation of important cell cycle regulators.
The analysis of transcription of immediate-early genes in undifferentiated cells has shown that c-fos and c-jun genes
are strongly activated by serum, and that ERK-kinase plays the main role in activation of c-fos transcription, while activation
of c-jun transcription depends predominantly on p38-kinase. It is necessary to note that PI3-kinase inhibitor increases effect
of serum stimulation of c-fos promoter. It means that the PI3-kinase dependent cascade negatively influences the cascade, which
activates c-fos transcription. Thus, the transcription of c-fos and c-jun is not connected with of EC F9 cell proliferation.
The proliferation of these cells depends on PI3-kinase activity.
Key words: F9 teratocarcinoma cells, proliferation, MAP-kinases, PI3-kinase
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