Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Paper
  • Published:

PKCη enhances cell cycle progression, the expression of G1 cyclins and p21 in MCF-7 cells

Oncogene volume 20, pages 6794–6804 (2001)Cite this article

Abstract

Protein kinase C encodes a family of enzymes implicated in cellular differentiation, growth control and tumor promotion. However, not much is known with respect to the molecular mechanisms that link protein kinase C to cell cycle control. Here we report that the expression of PKCη in MCF-7 cells, under the control of a tetracycline-responsive inducible promoter, enhanced cell growth and affected the cell cycle at several points. The induced expression of another PKC isoform, PKCδ, in MCF-7 cells had opposite effects and inhibited their growth. PKCη expression activated cellular pathways in these cells that resulted in the increased expression of the G1 phase cyclins, cyclin D and cyclin E. Expression of the cyclin-dependent kinase inhibitor p21WAF1 was also specifically elevated in PKCη expressing cells, but its overall effects were not inhibitory. Although, the protein levels of the cyclin-dependent kinase inhibitor p27KIP1 were not altered by the induced expression of PKCη, the cyclin E associated Cdk2 kinase activity was in correlation with the p27KIP1 bound to the cyclin E complex and not by p21WAF1 binding. PKCη expression enhanced the removal of p27KIP1 from this complex, and its re-association with the cyclin D/Cdk4 complex. Reduced binding of p27KIP1 to the cyclin D/Cdk4 complex at early time points of the cell cycle also enhanced the activity of this complex, while at later time points the decrease in bound p21WAF1 correlated with its increased activity in PKCη-expressing cells. Thus, PKCη induces altered expression of several cell cycle functions, which may contribute to its ability to affect cell growth.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

References

  • Agrawal D, Dong KF, Wang YZ, Kayda D, Pledjer WJ . 1995 Cell Growth Differ. 6: 1199–1205

  • Akashi M, Osawa W, Koeffler HP, Hachiya M . 1999 Biochem. J. 337: 607–616

  • Arita Y, Buffolino P, Coppock DL . 1998 Exp. Cell Res. 242: 381–390

  • Ashton AW, Watanabe G, Albanese C, Harrington EO, Ware JA, Pestell RG . 1999 J. Biol. Chem. 274: 20805–20811

  • Besson A, Yong VW . 2000 Mol. Cell. Biol. 20: 4580–4590

  • Brown LR, Nigh E, Lee RJ, Ye H, Thompson MA, Saudou F, Pestell RG, Greenberg ME . 1998 Mol. Cell. Biol. 18: 5609–5619

  • Cheng M, Olivier P, Dielh JA, Fero M, Roussel MF, Roberts JM . 1999 EMBO J. 18: 1571–1583

  • Choi PM, Tchou-Wong KM, Weinstein IB . 1990 Mol. Cell. Biol. 10: 4650–4657

  • Coppock DL, Tansey JB, Nathanson L . 1992 Cell Growth Diff. 3: 485–494

  • de Vente J, Kukoly CA, Bryant WO, Posekany KJ, Chen J, Fletcher DJ, Parker PJ, Pettit GJ, Lozano G, Cook PP, Ways DK . 1995 J. Clin. Invest. 96: 1874–1886

  • Downward J . 1997 Curr. Biol. 7: R258–R260

  • Eldar H, Zisman Y, Ullrich A, Livneh E . 1990 J. Biol. Chem. 265: 13290–13296

  • Fishman D, Segal S, Livneh E . 1998 Inter. J. Oncol. 12: 181–186

  • Frey MR, Saxon ML, Zhao X, Rollins A, Evans SS, Black JD . 1997 J. Biol. Chem. 272: 9424–9435

  • Fukumoto S, Nishizawa Y, Hosoi M, Koyama H, Yamakawa K, Ohno S, Morii H . 1997 J. Biol. Chem. 272: 13816–13822

  • Gossen M, Bujard H . 1992 Proc. Natl. Acad. Sci. USA 89: 5547–5551

  • Gruber JR, Ohno S, Niles RM . 1992 J. Biol. Chem. 267: 13356–13360

  • Hamada K, Takuwa N, Zhou W, Kumada M, Takuwa Y . 1996 Biochem. Biophys. Acta. 1310: 149–156

  • Harrington EO, Loffler J, Nelson PR, Kent KC, Simons M, Ware JA . 1997 J. Biol. Chem. 272: 7390–7397

  • Hass R, Gunji H, Hirano M, Weichselbaum R, Kufe D . 1993 Cell Growth Diff. 4: 159–166

  • Hiyama H, Iavarone A, Reeves SA . 1998 Oncogene 16: 1513–1523

  • Housey GM, Johnson MD, Hsiao WL, O'brian CA, Murphy JP, Kirschmeier P, Weinstein IB . 1988 Cell 52: 343–354

  • Hunter T, Pines J . 1994 Cell 79: 573–582

  • Hussaini IM, Karns LR, Vinton G, Carpenter JE, Redpath GT, Sando JJ, Vandenberg SR . 2000 J. Biol. Chem. 275: 22348–22354

  • Jaken S . 1996 Curr. Opin. Cell Biol. 8: 168–173

  • Kindregan HC, Rosenbaum SE, Ohno S, Niles RN . 1994 J. Biol. Chem. 269: 27756–27761

  • Koff A, Giordano A, Desai K, Yamashita K, Harper JW, Elledge S, Nishimoto T, Morgan DO, Franza RB, Roberts JM . 1992 Science 257: 1689–1694

  • LaBaer J, Garrett MD, Stevenson LF, Slingerland JM, Sandhu C, Chou HS, Fattaey A, Harlow E . 1997 Genes Dev. 11: 847–862

  • Lavoie JN, L'Allemain G, Brunet A, Muller R, Pouyssegur J . 1996 J. Biol. Chem. 271: 20608–20616

  • Livneh E, Fishman DD . 1997 Eur. J. Biochem. 248: 1–9

  • Livneh E, Shimon T, Bechor E, Doki Y, Schieren I, Weinstein IB . 1996 Oncogene 12: 1545–1555

  • Macleod KF, Sherry N, Hannon G, Beach D, Tokino T, Kinzler K, Vogelstein B, Jacks T . 1995 Genes Dev. 9: 935–944

  • Mantel C, Luo Z, Canfield J, Braun S, Deng C, Broxmeyer HE . 1996 Blood 88: 3710–3719

  • Mellor H, Parker PJ . 1998 Biochem. J. 332: 281–292

  • Michieli P, Chedid M, Lin D, Pierce JH, Mercer WE, Givol D . 1994 Cancer Res. 54: 3391–3395

  • Mischak H, Goodnight J, Kolch W, Martiny-Baron G, Scaechtle C, Kazanietz MG, Blumberg PM, Pierce JH, Mushinski JF . 1993 J. Biol. Chem. 268: 6090–6096

  • Nakaigawa N, Hirai S, Mizuno K, Shuin T, Hosaka M, Ohno S . 1996 Biochem. Biophys. Res. Commun. 222: 95–100

  • Newton AC . 1997 Curr. Opin. Cell Biol. 9: 161–167

  • Nishizuka Y . 1992 Science 258: 607–614

  • Nishizuka Y . 1995 FASEB J. 9: 484–496

  • Nourse J, Firpo E, Flanagan WM, Coats S, Polyak K, Lee MH, Massague J, Crabtree GR, Roberts JM . 1994 Nature 372: 570–573

  • Ohba M, Ishino K, Kashiwagi M, Kawabe S, Chida K, Huh N, Kuroki T . 1998 Mol. Cell. Biol. 18: 5199–5207

  • Parekh DB, Ziegler W, Parker PJ . 2000 EMBO J. 19: 496–503

  • Planas-Silva MD, Weinberg RA . 1997 Mol. Cell. Biol. 17: 4059–4069

  • Polyak K, Kato J, Solomon MJ, Sherr CJ, Massague J, Roberts JM, Koff A . 1994a Genes Dev. 8: 9–22

  • Polyak K, Lee MH, Erdjument-Bromage H, Koff A, Roberts JM, Tempst P, Massague J . 1994b Cell 78: 59–66

  • Reynisdottir I, Polyak K, Iavarone A, Massague J . 1995 Genes Dev. 9: 1831–1845

  • Sasaguri T, Kosaka C, Hirata M, Masuda J, Shimokado K, Fujishima M, Ogata J . 1993 Exp. Cell Res. 208: 311–320

  • Sherr CJ . 1994 Cell 79: 551–555

  • Sherr CJ, Roberts JM . 1999 Genes Dev. 13: 1501–1512

  • Slosberg ED, Klein MG, Yao Y, Han EK, Schieren I, Weinstein IB . 1999 Oncogene 18: 6658–6665

  • Soos T, Kiyokawa JH, Yan JS, Rubin MS, Giordano A, deBlasio A, Bottega S, Wong B, Mendelshon J, Koff A . 1996 Cell Growth Differ. 7: 135–146

  • Takenaka I, Morin F, Seizinger BR, Kley N . 1995 J. Biol. Chem. 270: 5405–5411

  • Thompson LJ, Fields AP . 1996 J. Biol. Chem. 271: 15045–15053

  • Watanabe T, Ono Y, Taniyama Y, Hazama K, Igarashi K, Ogita K, Kikkawa U, Nishizuka Y . 1992 Proc. Natl. Acad. Sci. USA 89: 10159–10163

  • Ways DK, Kukoly CA, deVente J, Hooker JL, Bryant WO, Posekany KJ, Fletcher DJ, Cook PP, Parker PJ . 1995 J. Clin. Invest. 95: 1906–1915

  • Weinberg RA . 1995 Cell 81: 323–330

  • Winston JT, Coats SR, Wang YZ, Pledger WJ . 1996 Oncogene 12: 127–134

  • Yamaguchi K, Ogita K, Nakamura S, Nishizuka Y . 1995 Biochem. Biophys. Res. Commun. 210: 639–647

  • Zeng YX, El-Deiry WS . 1996 Oncogene 12: 1557–1564

  • Zezula J, Dexl V, Hutter C, Karel A, Schutz W, Freissmuth M . 1997 J. Biol. Chem. 272: 29967–29974

  • Zhang H, Hannon GH, Beach D . 1994 Genes Dev. 8: 1750–1758

  • Zhou W, Takuwa N, Kumada M, Takuwa Y . 1993 J. Biol. Chem. 268: 23041–23048

Download references

Acknowledgements

This work was supported by a grant 97-00165 from the US–Israel Binational Science Fund, Jerusalem, by The Israel Cancer Association and the Israel Ministry of Health.

Author information

Authors and Affiliations

  1. Department of Microbiology and Immunology, Faculty of Health Sciences, Ben Gurion University, Beer Sheva, 84105, Israel

    Eyal Fima, Marat Shtutman, Pazit Libros, Adva Missel, Galit Shahaf, Galia Kahana & Etta Livneh

Authors
  1. Eyal Fima
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marat Shtutman
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Pazit Libros
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Adva Missel
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Galit Shahaf
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Galia Kahana
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Etta Livneh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Etta Livneh.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fima, E., Shtutman, M., Libros, P. et al. PKCη enhances cell cycle progression, the expression of G1 cyclins and p21 in MCF-7 cells. Oncogene 20, 6794–6804 (2001). https://doi.org/10.1038/sj.onc.1204885

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1204885

Keywords

This article is cited by

Search

Advanced search

Quick links