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:

Altered Ets transcription factor activity in prostate tumor cells inhibits anchorage-independent growth, survival, and invasiveness

Oncogene volume 19, pages 5507–5516 (2000)Cite this article

Abstract

The Ets family of transcription factors are important downstream targets in cellular transformation, as altering Ets activity has been found to reverse the transformed phenotype of Ras transformed mouse fibroblasts and of several human tumor cell lines. To determine whether Ets factors are important targets in the largely uncharacterized aberrant signaling in prostate cancer, we have altered Ets activity in the prostate tumor cell line PPC-1, by stable expression of either full-length Ets2, or a dominant inhibitor of Ets activity, the Ets2 DNA binding domain (Ets2DBD). Analysis of multiple independent clonal cell lines revealed that expression of either Ets2 or the Ets2DBD inhibited the anchorage-independent growth of PPC-1 cells up to 20-fold. In contrast to our previous findings with Ras-transformed NIH3T3 cells, PPC-1 cell lines expressing either Ets2 or the EtsDBD exhibited slower attached cell growth, increased Ets-dependent gene expression, and up to a 10-fold increase in apoptotic cell death. The p21cip gene was identified as a potential target of altered Ets signaling. Interestingly, the two distinct Ets2 constructs had strikingly different effects on in vitro invasiveness. Expression of the Ets2DBD almost completely blocked PPC-1 cell invasion through Matrigel, whereas overexpression of full-length Ets2 did not inhibit invasion. Overall, these results demonstrate that the balance of Ets factor activity can regulate multiple aspects of the transformed phenotype of PPC-1 prostate tumor cells, including anchorage-independent growth, survival, and invasiveness.

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

  • Beier F, Taylor AC and LuValle P. . 1999 J. Biol. Chem. 274: 30273–30279.

  • Borden P and Heller RA. . 1997 Crit. Rev. Eukaryotic Gene Expression 7: 159–178.

  • Borner MM, Myers CE, Sartor O, Sei Y, Toko T, Trepel JB and Schneider E. . 1995 Cancer Res. 55: 2122–2128.

  • Brothman AR, Lesho LJ, Somers KD, Wright Jr GL and Merchant DJ. . 1989 Int. J. Cancer 44: 898–903.

  • Brothman AR, Wilkins PC, Sales EW and Somers KD. . 1991 J. Urol. 145: 1088–1091.

  • Chen TR. . 1993 Cytogen. Cell Gen. 62: 183–184.

  • Chen G, Branton PE and Shore GC. . 1995 Exper. Cell Res. 221: 55–59.

  • Chen Z, Fisher RJ, Riggs CW, Rhim JS and Lautenberger JA. . 1997 Cancer Res. 57: 2013–2019.

  • Clark GJ, Cox AD, Graham SM and Der CJ. . 1995 Methods Enzymol. 255: 395–412.

  • Crawford HC and Matrisian LM. . 1996 Enzyme. Protein 49: 20–37.

  • Delannoy-Courdent A, Mattot V, Fafeur V, Fauquette W, Pellet I, Calmels T, Vercamer C, Boilly B, Vandenbunder B and Desbiens X. . 1998 J. Cell Sci. 111: 1521–1534.

  • Dittmer J and Nordheim A. . 1998 Biochim. Biophys. Acta 1377: F1-F11.

  • Foos G, García-Ramírez JJ, Galang CK and Hauser CA. . 1998 J. Biol. Chem. 273: 18871–18880.

  • Funaoka K, Shindoh M, Yoshida K, Hanzawa M, Hida K, Nishikata S and Fujinaga K. . 1997 Biochem. Biophys. Res. Commun. 236: 79–82.

  • Galang CK, Der CJ and Hauser CA. . 1994 Oncogene 9: 2913–2921.

  • Galang CK, Garcia-Ramirez J, Solski PA, Westwick JK, Der CJ, Neznanov NN, Oshima RG and Hauser CA. . 1996 J. Biol. Chem. 271: 7992–7998.

  • Ghysdael J and Boureux A. . 1997 The Ets family of transcriptional regulators. Oncogenes as Transcriptional Regulators, Vol. 1: Retroviral Oncogenes. Yaniv M and Ghysdael J (eds). Birkäuser Verlag: Basel, pp. 29–88.

  • Graves BJ and Petersen JM. . 1998 Advances in Cancer Research 75: 1–55.

  • Gumerlock PH, Poonamallee UR, Meyers FJ and de Vere White RW. . 1991 Cancer Res. 51: 1632–1637.

  • Hauser CA, Westwick JK and Quilliam LA. . 1995 Meth. Enzymol. 255: 412–426.

  • Huang CC, Papas TS and Bhat NK. . 1997 Oncogene 15: 851–856.

  • Huncharek M and Muscat J. . 1995 Cancer Epidemiol., Biomarkers Prev. 4: 681–687.

  • Konishi N, Hiasa Y, Tsuzuki T, Tao M, Enomoto T and Miller GJ. . 1997 Prostate 30: 53–57.

  • Kurada P and White K. . 1998 Cell 95: 319–329.

  • Langer SJ, Bortner DM, Roussel MF, Sherr CJ and Ostrowski MC. . 1992 Mol. Cell. Biol. 12: 5355–5362.

  • Li RH, Pei HP and Papas T. . 1999 Proc. Natl. Acad. Sci. USA 96: 3876–3881.

  • Liu AY, Corey E, Vessella RL, Lange PH, True LD, Huang GM, Nelson PS and Hood L. . 1997 Prostate 30: 145–153.

  • McCarthy SA, Chen D, Yang B-S, García-Ramírez JJ, Cherwinski H, Chen X-R, Klagsbrun ML, Hauser CA, Ostrowski MC and McMahon M. . 1997 Mol. Cell. Biol. 17: 2401–2412.

  • Rees S, Coote J, Stables J, Goodson S, Harris S and Lee MG. . 1996 Biotechniques 20: 102–110.

  • Royai R, Lange PH and Vessella R. . 1996 Semin. Oncol. 23: 35–40.

  • Sapi E, Flick MB, Rodov S and Kacinski BM. . 1998 Cancer Res. 58: 1027–1033.

  • Schneikert J, Peterziel H, Defossez PA, Klocker H, Launoit Y and Cato AC. . 1996 J. Biol. Chem. 271: 23907–23913.

  • Sementchenko VI, Schweinfest CW, Papas TS and Watson DK. . 1998 Oncogene 17: 2883–2888.

  • Sevilla L, Aperlo C, Dulic V, Chambard JC, Boutonnet C, Pasquier O and Boulukos KE. . 1999 Mol. Cell. Biol. 19: 2624–2634.

  • Shao NS, Chai YL, Cui JQ, Wang N, Aysola K, Reddy ESP and Rao VN. . 1998 Oncogene 17: 527–532.

  • Shi XB, Gumerlock PH and de Vere White RW. . 1996 World J. Urol. 14: 318–328.

  • Suzuki H, Romano-Spica V, Papas TS and Bhat NK. . 1995 Proc. Natl. Acad. Sci. USA 92: 4442–4446.

  • Wasilenko WJ, Palad AJ, Somers KD, Blackmore PF, Kohn EC, Rhim Jr. JS and Schellhammer PF. . 1996 Int. J. Cancer 68: 259–264.

  • Wasylyk B, Hagman J and Gutierrezhartmann A. . 1998 Trends Biochem. Sci. 23: 213–216.

  • Wasylyk C, Flores P, Gutman A and Wasylyk B. . 1989 EMBO J. 8: 3371–3378.

  • Wasylyk C, Maira SM, Sobieszczuk P and Wasylyk B. . 1994 Oncogene 9: 3665–3673.

  • Webber MM, Bello D and Quader S. . 1997 Prostate 30: 58–64.

  • Woods D, Parry D, Cherwinski H, Bosch E, Lees E and McMahon M. . 1997 Mol. Cell. Biol. 17: 5598–5611.

  • Yamada T, Kondoh N, Matsumoto M, Yoshida M, Maekawa A and Oikawa T. . 1997 Blood 89: 1383–1393.

  • Yang B-S, Hauser CA, Henkel G, Colman MS, Van Beveren C, Stacey KJ, Hume DA, Maki RA and Ostrowski MC. . 1996 Mol. Cell. Biol. 16: 538–547.

  • Zeng YX, Somasundaram K and Eldeiry WS. . 1997 Nature Genet. 15: 78–82.

  • Zhang M, Magit D and Sager R. . 1997 Proc. Natl. Acad. Sci. USA 94: 5673–5678.

Download references

Acknowledgements

This work was supported by National Institutes of Health Grants CA63130 and CA74547, and a postdoctoral fellowship to G Foos from the US Army Medical Research and Material Command. We thank RG Oshima for helpful discussions, and C Galang for excellent technical assistance.

Author information

Authors and Affiliations

  1. La Jolla Cancer Research Center, The Burnham Institute, La Jolla, 92037, California, CA, USA

    Gabriele Foos & Craig A Hauser

Authors
  1. Gabriele Foos
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Craig A Hauser
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Foos, G., Hauser, C. Altered Ets transcription factor activity in prostate tumor cells inhibits anchorage-independent growth, survival, and invasiveness. Oncogene 19, 5507–5516 (2000). https://doi.org/10.1038/sj.onc.1203946

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1203946

Keywords

This article is cited by

Search

Advanced search

Quick links