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:

Paired-Box genes are frequently expressed in cancer and often required for cancer cell survival

Oncogene volume 22, pages 7989–7997 (2003)Cite this article

Abstract

The paired-box (PAX) genes encode a family of nine well-characterized paired-box transcription factors, with important roles in development and disease. Although PAX genes are primarily expressed in the embryo, constitutive expression promotes tissue hyperplasia. Rare tumor-specific mutations of PAX genes implicate an oncogenic role, and persistent PAX expression characterizes several tumors. Yet, a cancer-wide analysis of PAX gene expression to investigate a general role for PAX genes has not been performed. We analysed the pattern and requirement for PAX gene expression in a panel of common cancer cell lines. Very frequent PAX gene expression was identified in tumor cell lines, including lymphoma, breast, ovarian, lung, and colon cancer. In addition, the PAX2 gene was frequently expressed in a panel of 406 common primary tumor tissues. Apoptosis was rapidly induced in ovarian and bladder cancer cell lines following RNA interference to silence PAX2 expression, despite concomitant TP53 and/or HRAS mutations. These data suggest that PAX genes are frequently expressed in cancer, and that endogenous PAX gene expression is required for the growth and survival of cancer cells.

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
Figure 6

Similar content being viewed by others

References

  • Barr FG, Galili N, Holick J, Biegel JA, Rovera G and Emanuel BS . (1993). Nat. Genet., 3, 113–117.

  • Barton K, Leiden JM and Margue CM . (2000). Dev. Biol., 222, 110–123.

  • Bender CM, Gonzalgo ML, Gonzales FA, Nguyen CT, Robertson KD and Jones PA . (1999). Mol. Cell. Biol., 19, 6690–6698.

  • Bernasconi M, Remppis A, Fredericks III WJ, FJR and Schafer BW . (1996). Proc. Natl. Acad. Sci. USA, 93, 13164–13169.

  • Borycki AG, Li J, Jin F, Emerson CP and Epstein JA . (1999). Development, 126, 1665–1674.

  • Bouchard M, Pfeffer P and Busslinger M . (2000). Development, 127, 3703–3713.

  • Bouchard M, Souabni A, Mandler M, Neubuser A and Busslinger M . (2002). Genes Dev., 16, 2958–2970.

  • Cazzaniga G, Daniotti M, Tosi S, Giudici G, Aloisi A, Pogliani E, Kearney L and Biondi A . (2001). Cancer Res., 61, 4666–4670.

  • Chi N and Epstein JA . (2002). Trends Genet., 18, 41–47.

  • Dahl E, Koseki H and Balling R . (1997). BioEssays, 19, 755–765.

  • Davis RJ, D’Cruz CM, Lovell MA, Biegel JA and Barr FG . (1994). Cancer Res., 54, 2869–2872.

  • Dressler GR and Douglass EC . (1992). Proc. Natl. Acad. Sci. USA, 89, 1179–1183.

  • Dressler GR, Wilkinson JE, Rothenpieler UW, Patterson LT, Williams-Simons L and Westphal H . (1993). Nature, 362, 65–67.

  • Eccles MR . (1998). Ped. Nephrol., 12, 712–720.

  • Eccles MR, Wallis LJ, Fidler AE, Spurr NK, Goodfellow PJ and Reeve AE . (1992). Cell Growth Differ., 3, 279–289.

  • Eccles MR, Yun K, Reeve AE and Fidler AE . (1995). Am. J. Pathol., 146, 40–45.

  • Fabbro D, Di-Loreto C, Beltrami CA, Belfiore A, Di-Lauro R and Damante G . (1994). Cancer Res., 54, 4744–4749.

  • Fickenscher HR, Chalepakis G and Gruss P . (1993). DNA Cell Biol., 12, 381–391.

  • Glaser T, Walton DS and Maas RL . (1992). Nat. Genet., 2, 232–238.

  • Gnarra JR and Dressler GR . (1995). Cancer Res., 55, 4092–4098.

  • Hewitt SM, Hamada S, Monarres A, Kottical LV, Saunders GS and McDonnell TJ . (1997). Anticancer Res., 17, 3211–3216.

  • Jordan T, Hanson I, Zaletayev D, Hodgson S, Prosser J, Seawright A, Hastie N and van Heyningen V . (1992). Nat. Genet., 1, 328–332.

  • Kozmik Z, Kurzabauer R, Dorfler P and Busslinger M . (1993). Mol. Cell. Biol., 13, 6024–6035.

  • Kroll TG, Sarraf P, Pecciarini L, Chen CJ, Mueller E, Spiegelman BM and Fletcher JA . (2000). Science, 289, 1357–1360.

  • Lin TK, Hughes G, Muratovska A, Blaikie FH, Brookes PS, Darley-Usmar V, Smith RA and Murphy MP . (2002). J. Biol. Chem., 277, 17048–17056.

  • Mansouri A and Gruss P . (1998). Mech. Dev., 78, 171–178.

  • Margue CM, Bernasconi M, Barr FG and Schafer BW . (2000). Oncogene, 19, 2921–2929.

  • Marques AR, Espadinha C, Catarino AL, Moniz S, Pereira T, Sobrinho LG and Leite V . (2002). J. Clin. Endocrinol. Metab., 87, 3947–3952.

  • Morrison AM, Jäger U, Chott A, Schebesta M, Haas OA and Busslinger M . (1998a). Blood, 92, 3865–3878.

  • Morrison AM, Nutt SL, Thevenin C, Rolink A and Busslinger M . (1998b). Semin. Immunol., 10, 133–142.

  • Murer L, Caridi G, Della Vella M, Montini G, Carasi C, Ghiggeri G and Zacchello G . (2002). Nephron, 91, 588–593.

  • Ostrom L, Tang MJ, Gruss P and Dressler GR . (2000). Dev. Biol., 219, 250–258.

  • Parada LF, Tabin CJ, Shih C and Weinberg RA . (1982). Nature, 297, 474–478.

  • Pfeffer PL, Gerster T, Lun K, Brand M and Busslinger M . (1998). Development, 125, 3063–3074.

  • Porteous S, Torban E, Cho NP, Cunliffe H, Chua L, McNoe L, Ward T, Souza C, Gus P, Giugliani R, Sato T, Yun K, Favor J, Sicotte M, Goodyer P and Eccles M . (2000). Hum. Mol. Genet., 9, 1–11.

  • Ridgeway AG and Skerjanc IS . (2001). J. Biol. Chem., 276, 19033–19039.

  • Rieger KM, Little AF, Swart JM, Kastrinakis WV, Fitzgerald JM, Hess DT, Libertino JA and Summerhayes IC . (1995). Br. J. Cancer, 72, 683–690.

  • Ross DT, Scherf U, Eisen MB, Perou CM, Rees C, Spellman P, Iyer V, Jeffrey SS, Van de Rijn M, Waltham M, Pergamenschikov A, Lee JC, Lashkari D, Shalon D, Myers TG, Weinstein JN, Botstein D and Brown PO . (2000). Nat. Genet., 24, 227–235.

  • Salem CE, Markl ID, Bender CM, Gonzales FA, Jones PA and Liang G . (2000). Int. J. Cancer, 87, 179–185.

  • Sanyanusin P, Schimmenti LA, McNoe LA, Ward TA, Pierpont MEM, Sullivan MJ, Dobyns WB and Eccles MR . (1995). Nat. Genet., 9, 358–363.

  • Scholl FA, Kamarashev J, Murmann OV, Geertsen R, Dummer R and Schafer BW . (2001). Cancer Res., 61, 823–826.

  • Silberstein GB, Dressler GR and Van Horn K . (2002). Oncogene, 21, 1009–1016.

  • St-Onge L, Sosa-Pineda B, Chowdhury K, Mansouri A and Gruss P . (1997). Nature, 387, 406–409.

  • Steinbach JP, Kozmik Z, Pfeffer P and Aguzzi A . (2001). Int. J. Cancer, 93, 459–467.

  • Stuart ET, Haffner R, Oren M and Gruss P . (1995a). EMBO J., 14, 5638–5645.

  • Stuart ET, Kioussi C, Aguzzi A and Gruss P . (1995b). Clin. Cancer Res., 1, 207–214.

  • Tassabehji M, Read AP, Newton VE, Harris R, Balling R, Gruss P and Strachan T . (1992). Nature, 355, 635–636.

  • Torban E, Eccles M, Favor, J. and Goodyer and P . (2000). Am. J. Pathol., 157, 833–842.

  • van Raamsdonk CD and Tilghman SM . (2000). Development, 127, 5439–5448.

  • Winyard PJD, Risdon RA, Sams VR, Dressler GR and Woolf AS . (1996). J. Clin. Invest., 98, 451–459.

Download references

Acknowledgements

We thank A Kao for technical assistance. Tissue samples were provided by the Cooperative Human Tissue Network, which is funded by the National Cancer Institute. NCI-60 tumor cell lines were obtained from the Developmental Therapeutics Program, National Cancer Institute. This work was supported by grants from the Cancer Society, Health Research Council, Lottery Health Board of New Zealand, and MedTech Partners (Quebec) Inc. MRE was supported by a James Cook Research Fellowship of the Royal Society of New Zealand.

Author information

Authors and Affiliations

  1. Department of Pathology, Dunedin School of Medicine, University of Otago, PO Box 913, Dunedin, New Zealand

    Aleksandra Muratovska, Chaoming Zhou, Shuji He & Michael R Eccles

  2. Department of Pediatrics, McGill University, Montreal Children's Hospital Research Institute, 4060 St Catherine Street West, Westmount, H3Z2Z3, Quebec, Canada

    Paul Goodyer

Authors
  1. Aleksandra Muratovska
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chaoming Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shuji He
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Paul Goodyer
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Michael R Eccles
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michael R Eccles.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Muratovska, A., Zhou, C., He, S. et al. Paired-Box genes are frequently expressed in cancer and often required for cancer cell survival. Oncogene 22, 7989–7997 (2003). https://doi.org/10.1038/sj.onc.1206766

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1206766

Keywords

This article is cited by

Search

Advanced search

Quick links