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Cell cycle genes as targets of retinoid induced ovarian tumor cell growth suppression

Oncogene volume 20, pages 7935–7944 (2001)Cite this article

Abstract

We have examined the effect of all-trans-retinoic acid (RA) on cell cycle gene expression in RA sensitive CA-OV3 and RA resistant SK-OV3 ovarian carcinoma cell lines. Gene expression was analysed by multiprobe RNAse protection, Western blotting and in vitro kinase assays. No differences were observed between RA sensitive and RA resistant ovarian carcinoma cells in the levels of expression of many cell cycle genes including cyclin A, B and E, cdk 2,4 and 6, E2F-1, E2F-2, E2F-3, E2F-4, E2F-5, DP-1 and DP-2. However, RA sensitive CA-OV3 cells expressed higher levels of p53, p27, p21, and p16 compared to RA resistant SK-OV3 cells. In addition, RA treatment of CA-OV3 cells resulted in a significant decrease in hyperphosphorylated RB and RB-2/p130 and corresponding significant increases in the levels of hypophosphorylated and/or partially phosphorylated RB-2/p130 protein and hypophosphorylated RB. Also, RA treatment increased expression of the cdk inhibitor p27 and decreased activity of cdk 2, cdk 4 and cdk 6. Finally, amounts of p27-cyclin E and RB-2/p130-E2F4 complexes were found to increase in CA-OV3 cells growth arrested by RA. These results suggest that the pocket protein pathways are critical targets for retinoid suppression of ovarian carcinoma cell growth.

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References

  • Baldassarre G, Boccia A, Bruni P, Sandomenico C, Barone MV, Pepe S, Angrisano T, Belletti B, Motti ML, Fusco A, Viglietto G . 2000 Cell Growth Differ. 11: 517–526

  • Baldi A, De Luca A, Claudio PP, Baldi F, Giordano GG, Tommasino M, Paggi MG, Giordano A . 1995 J. Cell Biochem. 59: 402–408

  • Borriello A, Pietra VD, Criscuolo M, Oliva A, Tonini GP, Iolascon A, Zappia V, Ragione FD . 2000 Oncogene 19: 51–60

  • Buchkovich K, Duffy LA, Harlow E . 1989 Cell 58: 1097–1105

  • Caliaro MJ, Marmouget C, Guichard S, Mazars P, Valette A, Moisand A, Bugat R, Jozan S . 1994 Int. J. Cancer 56: 743–748

  • Chao WR, Hobbs PD, Jong L, Zhang XK, Zheng Y, Wu Q, Shroot B, Dawson MI . 1997 Cancer Letters 115: 1–7

  • Chen PL, Scully P, Shew JY, Wang JY, Lee WH . 1989 Cell 58: 1193–1198

  • Claudio PP, De Luca A, Howard CM, Baldi A, Firpo EJ, Koff A, Paggi MG, Giordano A . 1996 Cancer Research 56: 2003–2008

  • Daly M, Obrams GI . 1998 Semin. Oncol. 25: 255–264

  • Dannenberg JH, van Rossum A, Schuijff L, te Riele H . 2000 Genes and Development 14: 3051–3064

  • DeCaprio JA, Ludlow JW, Lynch D, Furukawa Y, Griffin J, Piwnica-Worms H, Huang CM, Livingston DM . 1989 Cell 58: 1085–1095

  • Giordano A, Lee J, Scheppler JA, Herrmann C, Harlow E, Deuschle U, Beach D, Franza BR . 1991 Science 25: 1271–1275

  • Greenlee RT, Hill-Harmon MB, Murray T, Thun M . 2001 CA Cancer J. Clin. 51: 15–36

  • Grunt TW, Somay C, Ellinger A, Pavelka M, Dittrich E, Dittrich C . 1992a J. Cell. Physiol. 151: 13–22

  • Grunt TW, Somay C, Oeller H, Dittrich E, Dittrich C . 1992b J. Cell Sci. 103: 501–509

  • Grunt TW, Somay C, Pavelka M, Ellinger A, Dittrich E, Dittrich C . 1991 J. Cell Sci. 100: 657–666

  • Hannon GJ, Demetrick D, Beach D . 1993 Genes Dev. 7: 2378–2391

  • Hoskins WJ . 1995 J. Cell. Biochem. 59: 189–199

  • Hsu CA, Rishi AK, Su-Li X, Gerald TM, Dawson MI, Schiffer C, Reichert U, Shroot B, Poirer GC, Fontana JA . 1997 Blood 89: 4470–4479

  • Landis SH, Murray T, Bolden S, Wingo PA . 1998 CA Cancer J. Clin. 48: 6–29

  • Li Y, Graham C, Lacy S, Duncan AM, Whyte P . 1993 Genes Dev. 7: 2366–2377

  • Li Y, Lin B, Agadir A, Liu R, Dawson MI, Reed JC, Fontana JA, Bost F, Hobbs PD, Zheng Y, Chen GQ, Shroot B, Mercola D, Zhang XK . 1998 Mol. Cell. Biol. 18: 4719–4731

  • Mangelsdorf DJ, Umesono K, Evans RM . 1994 The Retinoids, 2nd edn. Sporn MB, Roberts AB, Goodman DS (eds). New York: Raven Press pp 319–350

  • Matsuo T, Thiele CJ . 1998 Oncogene 16: 3337–3343

  • Mayol X, Grana X, Baldi A, Sang N, Hu Q, Giordano A . 1993 Oncogene 8: 2561–2566

  • Mayol X, Garriga J, Grana X . 1995 Oncogene 11: 801–808

  • Mayol X, Garriga J, Grana X . 1996 Oncogene 13: 237–246

  • Mayol X, Grana X . 1997 Prog. Cell Cycle Res. 3: 157–169

  • Mihara K, Cao XR, Yen A, Chandler S, Driscoll B, Murphree AL, T'Ang A, Fung YK . 1989 Science 246: 1300–1303

  • Mittnacht S . 1998 Curr. Opin. Genet. Dev. 8: 21–27

  • Naderi S, Blomhoff HK . 1999 Blood 94: 1348–1358

  • Nevins JR . 1998 Cell Growth Differ. 9: 585–593

  • Paggi MG, Baldi A, Bonetto F, Giordano A . 1996 J. Cell Biochem. 62: 418–430

  • Sage J, Mulligan GJ, Attardi LD, Miller A, Chen S, Williams B, Theodorou E, Jacks T . 2000 Genes Develop. 14: 3037–3050

  • Seewaldt VL, Kim JH, Parker MB. Dietze EC, Srinivasan KV, Caldwell LE . 1999 Exp. Cell. Res. 249: 70–85

  • Slingerland J, Pagano M . 2000 J. Cell. Physiol. 183: 10–17

  • Sidle A, Palaty C, Dirks P, Wiggan O, Kiess M, Gill RM, Wong AK, Hamel PA . 1996 Crit. Rev. Biochem. Mol. Biol. 31: 237–271

  • Soprano DR, Chen LX, Wu S, Donigan AM, Borghaei RC, Soprano KJ . 1996 Oncogene 12: 577–584

  • Spinella MJ, Freemantle SJ, Sekula D, Chang JH, Christie AJ, Dmitrovsky E . 1999 J. Biol. Chem. 274: 22013–22018

  • Sueoka N, Lee HY, Walsh GL, Hong WK, Kurie JM . 1999 Cancer Res. 59: 3838–3844

  • Teixeira C, Pratt MA . 1997 Mol. Endocrinol. 11: 1191–1202

  • Watanabe Y, Watanabe T, Kitagawa M, Taya Y, Nakayama K, Motoyama N . 1999 Brain Res. 842: 342–350

  • Weber E, Ravi RK, Knudsen ES, Williams JR, Dillehay LE, Nelkin BD, Kalemkerian GP, Feramisco JR, Mabry M . 1999 Int. J. Cancer 80: 935–943

  • Wilcken NR, Sarcevic B, Musgrove EA, Sutherland RL . 1996 Cell Growth Differ. 7: 65–74

  • Wu S, Donigan A, Platsoucas CD, Jung W, Soprano DR, Soprano KJ . 1997a Exp. Cell Res. 232: 277–286

  • Wu S, Zhang ZP, Zhang D, Soprano DR, Soprano KJ . 1997b Exp. Cell Res. 237: 118–126

  • Wu S, Zhang D, Donigan A, Dawson MI, Soprano DR, Soprano KJ . 1998a J. Cell Biochem. 68: 378–388

  • Wu S, Zhang D, Zhang ZP, Soprano DR, Soprano KJ . 1998b Oncogene 17: 2839–2849

  • Zancai P, Cariati R, Rizzo S, Boiocchi M, Dolcetti R . 1998 Oncogene 17: 1827–1836

  • Zhang D, Holmes WF, Wu S, Soprano DR, Soprano KJ . 2000 J. Cell. Physiol. 185: 1–20

  • Zhou Q, Stetler-Stevenson M, Steeg PS . 1997 Oncogene 15: 107–115

  • Zhu WY, Jones CS, Kiss A, Matsukuma K, Amin S, DeLuca LM . 1997 Exp. Cell Res. 234: 293–299

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Acknowledgements

This work was supported by grants from the National Institutes of Health to KJ Soprano (DK 49045 and CA 64945) and A Giordano (CA 60999 and NS 36466). We thank Hoffman La-Roche and Co. for the all-trans-retinoic acid used in these studies.

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Authors and Affiliations

  1. Department of Microbiology & Immunology, Temple University School of Medicine, 3400 North Broad Street, Philadelphia, PA 19140, Pennsylvania, USA

    Dongmei Zhang, Scott Vuocolo & Kenneth J Soprano

  2. Department of Biochemistry, Temple University School of Medicine, Philadelphia, PA 19140, 3400 North Broad Street, Pennsylvania, USA

    Dianne Robert Soprano

  3. Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, 3400 North Broad Street, Philadelphia, PA 19140, Pennsylvania, USA

    Dianne Robert Soprano & Kenneth J Soprano

  4. Department of Pathology, Anatomy and Cell Biology, Jefferson Medical College, Philadelphia, PA 19107, Pennsylvania, USA

    Valeria Masciullo, Teodoro Sava & Antonio Giordano

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  1. Dongmei Zhang
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  2. Scott Vuocolo
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Correspondence to Dianne Robert Soprano.

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Zhang, D., Vuocolo, S., Masciullo, V. et al. Cell cycle genes as targets of retinoid induced ovarian tumor cell growth suppression. Oncogene 20, 7935–7944 (2001). https://doi.org/10.1038/sj.onc.1204971

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