Effect of Retinoic Acid and dibutyryl cyclic AMP on G1 Phase Associated Molecules during F9 Embryonic Carcinoma Cell Differentiation

Retinoic acid와 dibutyryl cyclic AMP가 F9 embryonic carcinoma cell 분화 중 G1 Phase 관련 분자에 미치는 영향

  • 박귀례 (식품의약품안전청, 국립독성연구소) ;
  • 김건홍 (세대학교) ;
  • 한순영 (식품의약품안전청, 국립독성연구소) ;
  • 이유미 (식품의약품안전청, 국립독성연구소) ;
  • 장성재 (식품의약품안전청, 국립독성연구소)
  • Published : 1999.06.01

Abstract

Retinoic acid (RA) and dibutyryl cyclic AMP (dbcAMP) induce the differentiation of the multipotent embryonic carcinoma cell line, F9 cells, into parietal endoderm like cell. The F9 cells are highly proliferative doubling approximately 12 hourse. S Phase is predominant, lasting 10 hours and G2/M phase occupies most of the remaining cycle (2 hours) and G1 phase is nearly non-existent. In this study, we showed the effect of RA and dbcAMPon the cell cycle associated molecules (especially around G1 phase) during F9 cell differentiation. Differentiation of F9 cells was induced by the combined addition of RA ($10^{-7}M$) and dbcAMP (0.5mM), and cells were harvested daily up to 4 days. Flow cytometric analysis showed the prolongation of G1 phase around 30 hours after induction. Western blot analysis revealed that the amount of cyclin D1 and cdk2 were increased at day 4. However, histone H1 kinase activity of cdk2 was decreased. These data strongly suggest that RA and dbcAMP induce the growth arrest of F9 cells at G1 phase by decreasing the activity of cdk2, although they have increased the protein contents of cyclin D1 and cdk2. The reason for the discrepancy between the H1 kinase activity and protein contents are not clear yet.

Keywords

References

  1. Cell v.15 The induction of differentiation in teratocarcinoma stem cells by retinoic acid Strickland,S.;Mahadavi,V.
  2. Exp. Cell Res v.124 Stimulation of differentiation of several murine embryonal carcinoma cell lines by retinoic acid Jetten,A.M.;Jetten,M.E.R.;Sherman,M.I.
  3. Cell v.21 Hormonal induction of differentiation in teratocarcinoma stem cells: generation of parietal endoderm by retinoic acid and dibutyryl cyclic AMP Strickland,S.;Smith,K.K.;Marotti,K.R.
  4. Cell v.124 The differentiation of teratocarcinoma stem cells is marked by the types of collagen which are synthethized Adamson,E.D.;Gaunt,S.J.;Graham,C.F.
  5. Science v.209 Teratocarcinomas and mammalian embryogenesis Martin,G.
  6. Nature v.291 Cell interactions modulate embryonal carcinoma cell differentiation into parietal or visceral endoderm Hogan,B.L.M.;Taylor,A.;Adamson,E.
  7. Dev. Biol. v.89 Cell cycle characteristics of undifferentiated and differentiated embryonal carcinoma cells Rosenstraus,M.J.;Sundell,C.L.;Liskay,R.M.
  8. Nature v.346 Human cyclin A is adenovirus E1A associated protein p60 and behaves differently from cyclin B Pines,J.;Hunter,T.
  9. Cell v.66 Isolation of three novel human cyclins by rescue of G1 cyclin (Cln) function in yeast Lew,D.J.;Dulic,V.;Reed,S.I.
  10. Cell v.65 Colony stimulating factor 1 regulates novel cyclins during the G1 phase of the cell cycle Matsushime,H.;Roussel,M.F.;Ashmun,R.A.;Sherr,C.J.
  11. Nature v.350 A novel cyclin encoded by a bcll-linked candidate oncogene Motokura,T.;Bloom,T.;Kim,H.G.;Juppner,H.;Ruderman,J.V.;Kronenberg,H.M.;Arnold,A.
  12. Cell v.65 Human D type cyclin Xiong,Y.;Connolly,T.;Futcher,B.;Beach,D.
  13. EMBO J. v.11 A family of human cdc-2 related protein kinases Meyerson,M.;Enders,G.H.;Wu,C.;Su,L.;Gorka,C.;Nelson,C.;Harlow,E.;Tsai,L.
  14. Trends Biochem. Sci. v.18 Cyclins and cyclin-dependent kinases: take your partners Pines,J.
  15. Trends Cell Biol v.1 Cyclin dependent kinases: a new cell cycle motif? Pines,J.;Hunter,T.
  16. Cell v.73 Mammalian, G1 cyclins Sherr,C.J.
  17. Ann. Rev. Biochem v.61 Animal cell cycles and their control Norbury,C.;Nurse,P.
  18. Cell v.67 Cyclin A is required for the onset of DNA replication in mammalian fibroblast Girard,F.;Strausfeld,U.;Fernandez,A.;Lamb,N.
  19. EMBO J. v.11 Cyclin A is required at two points in the human cell cycle Pagano,M.;Pepperkok,R.;Verde,F.;Ansorge,W.;Draetta,G.
  20. Biochem. Biophys. Res. Commun. v.182 Cyclin A is required in normal epithelial cells Zindy,F.;Lamas,E.;Chenivesse,X.;Sobczack,J.;Wang,J.;Fesquet,D.;Henglein,B.;Brechot,C.
  21. Genes Dev v.7 Cyclin D1 is a nuclear protein required for cell cycle progression in G1 Baldin,V;Likas,J.;Marcote,M.J.;Pagano,M.;Bartek,J.;Draetta,G.
  22. Science v.259 Cyclin dependent regulation of G1 in mammalian cells Ohtsubo,M.;Roverts,J.M.
  23. Genes Dev v.7 Overexpression of mouse D-type cyclins accelerates G1 phase in rodent fibroblasts Quelle,D.E.;Ashmun,R.A.;Shurtleff,S.A.;Kato,J.;Bar-Sagi,D.;Roussel,M.F.;Sherr,J.
  24. Cell v.58 The retinoblastoma protein is phosphorylated during specific phases of the cell cycle Buchkovich,K.;Duffy,L.A.;Harlow,E.
  25. Cell v.58 Phosphorylation of the retinoblastoma gene product is modulated during the cell cycle and cellualr differentiation Chen,P.L.;Scully,P.;Shew,J.Y.;Wang,J.Y.;Lee,W.H.
  26. Science v.246 Cell cycle dependent regulation of phosphorylation of the human retinoblastoma gene product Mihara,K.;Cao,X.R.;Yen,A.;Chandler,S.;Driscoll,B.;Murphree,A.L.;T'ang,A.;Fung,Y.K.
  27. Oncogene v.9 Contrasting patterns of retinoblastoma protein expression in mouse embryonic stem cells and embryonic fibroblasts Savatier,P.;Huang,S.;Szekely,L.;Wiman,K.G.;Samarut,J.
  28. J. Virol. v.65 Role of E2F transcription factor in E1A mediated transactivation of cellular genes Hiebert,S.W.;Blake,M.;Azizkhan,J.;Nevins,J.R.
  29. Mol. Cell. Biol. v.12 Transcriptional repression of the E2 containing promoters EⅡaE, c-myc, and RB1 by the product of the RB1 gene Hamel,P.A.;Gill,R.M.;Phillips,R.A.;Gallie,B.L.
  30. Exp. Cell. Res. v.164 Studies on the relation of DNA synthesis to retinoic acid induced differentiation of F9 teratocarcinoma cells Griep,A.E.;Deluca,H.F.
  31. Cytometry v.3 A detergent-trypsin method for the preparation of nuclei for flow cytometric DNA analysis Vindelov,L.L.;Christensen,I.B.J.;Nissen,N.I.
  32. Dev. Biol. v.89 Rosenstraus,M.J.;Sundel,C.L.;Liskay,R.M.
  33. Science v.257 Association of human cyclin E with a periodic G1-S phase protein kinase Dulic,V.;Lees,E.;Reed,S.I.
  34. Cell v.70 Regulation of retinoblastoma protein functions by ectopic expression of human cyclins Hinds,P.W.;Mittnacht,S.;Dulic,V.;Arnold,A.;Redd,S.I.;Weinberg,R.A.
  35. Proc. Natl. Acad. Sci. USA v.90 Altered regulation of G1 cyclins in senescent human diploid fibroblasts: Accumulation of inactive cyclin E-cdk2 and cyclin D1-ckd2 complexes Dulic,V.;Drullinger,L.F.;Lees,E.;Reed,S.I.;Stein,G.H.