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.

  • Oncogenomics
  • Published:

Expression profiling of microdissected pancreatic adenocarcinomas

Abstract

Pancreatic ductal adenocarcinoma is characterized by a paucity of neoplastic cells embedded in a densely desmoplastic stroma. Therefore, laser capture microdissection was performed to obtain homogeneous populations of normal and neoplastic ductal cells. These were subjected to a comparative study of gene expression utilizing human cDNA arrays. A variety of dysregulated genes were identified, comprising cell cycle and growth regulators, invasion regulators, signalling and developmental molecules. In addition to genes already found to be overexpressed in pancreatic cancer, such as TIMP1, MMP7, CD59, rhoC and NDKA, we present evidence to implicate genes which have not previously been reported in this tumour type. These include the overexpressed genes ABL2, Notch4 and SOD1, as well as XRCC1, a DNA repair gene whose transcript was found downregulated. Quantitative real-time RT–PCR (QRT–PCR) was employed to confirm differential expression of ABL2, Notch4 and SOD1 and immunohistochemical analysis was used to verify decreased protein expression of XRCC1 using a custom-built pancreatic tissue array. Combining microarray-derived gene expression profiles of pure pancreatic cell populations, QRT–PCR and pancreas-specific tissue arrays therefore proved to be highly informative in elucidating the molecular pathology of this highly malignant tumour type.

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

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

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

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  • Apelqvist A, Li H, Sommer L, Beatus P, Anderson DJ, Honjo T, Hrabe de Angelis M, Lendahl U, Edlund H . 1999 Nature 400: 877–881

  • Audic S, Claverie JM . 1997 Genome Res. 7: 986–995

  • Bankson DD, Kestin M, Rifai N . 1993 Clin. Lab. Med. 13: 463–480

  • Baskaran R, Chiang GG, Mysliwiec T, Kruh GD, Wang JY . 1997 J. Biol. Chem. 272: 18905–18909

  • Bonner RF, Emmert-Buck M, Cole K, Pohida T, Chuaqui R, Goldstein S, Liotta LA . 1997 Science 278: 1481–1483

  • Bramhall SR, Neoptolemos JP, Stamp GW, Lemoine NR . 1997 J. Pathol. 182: 347–355

  • Bramhall SR, Stamp GW, Dunn J, Lemoine NR, Neoptolemos JP . 1996 Br. J. Cancer 73: 972–978

  • Cazzaniga G, Tosi S, Aloisi A, Giudici G, Daniotti M, Pioltelli P, Kearney L, Biondi A . 1999 Blood 94: 4370–4373

  • Crnogorac-Jurcevic T, Efthimiou E, Capelli P, Blaveri E, Terris B, Baron A, Jones M, Tyson K, Bassi C, Scarpa A, Lemoine NR . 2001 Oncogene 20: 7437–7446

  • Crnogorac-Jurcevic T, Neilsen T, Lemoine N . 2002 Methods in Molecular Biology: RT–PCR Protocols O'Connell J (ed) Totowa NJ: Humana Press

  • Fitzgerald K, Harrington A, Leder P . 2000 Oncogene 19: 4191–4198

  • Furukawa T, Duguid WP, Rosenberg L, Viallet J, Galloway DA, Tsao MS . 1996 Am. J. Pathol. 148: 1763–1770

  • Gold EB . 1995 Surg. Clin. North Am. 75: 819–843

  • Gress TM, Muller-Pillasch F, Lerch MM, Friess H, Buchler M, Adler G . 1995 Int. J. Cancer 62: 407–413

  • Hruban RH, Wilentz RE, Kern SE . 2000 Am. J. Pathol. 156: 1821–1825

  • Huang P, Feng L, Oldham EA, Keating MJ, Plunkett W . 2000 Nature 407: 390–395

  • Imatani A, Callahan R . 2000 Oncogene 19: 223–231

  • Jhappan C, Gallahan D, Stahle C, Chu E, Smith GH, Merlino G, Callahan R . 1992 Genes Dev. 6: 345–355

  • Kallioniemi OP, Wagner U, Kononen J, Sauter G . 2001 Hum. Mol. Genet. 10: 657–662

  • Kononen J, Bubendorf L, Kallioniemi A, Barlund M, Schraml P, Leighton S, Torhorst J, Mihatsch MJ, Sauter G, Kallioniemi OP . 1998 Nat. Med. 4: 844–847

  • Kruh GD, Perego R, Miki T, Aaronson SA . 1990 Proc. Natl. Acad. Sci. USA 87: 5802–5806

  • Maio M, Brasoveanu LI, Coral S, Sigalotti L, Lamaj E, Gasparollo A, Visintin A, Altomonte M, Fonsatti E . 1998 Int. J. Oncol. 13: 305–318

  • Moore PS, Orlandini S, Zamboni G, Capelli P, Rigaud G, Falconi M, Bassi C, Lemoine NR, Scarpa A . 2001 Br. J. Cancer 84: 253–262

  • Oberley LW, Buettner GR . 1979 Cancer Res. 39: 1141–1149

  • Rice PA . 1999 Nat. Struct. Biol. 6: 805–806

  • Schmitt CA, Schwaeble W, Wittig BM, Meyer zum Buschenfelde KH, Dippold WG . 1999 Eur. J. Cancer 35: 117–124

  • Sirivatanauksorn V, Sirivatanauksorn Y, Gorman PA, Davidson JM, Sheer D, Moore PS, Scarpa A, Edwards PA, Lemoine NR . 2001 Int. J. Cancer 91: 350–358

  • Sirivatanauksorn Y, Drury R, Crnogorac-Jurcevic T, Sirivatanauksorn V, Lemoine NR . 1999 J. Pathol. 189: 150–154

  • Westman NG, Marklund SL . 1981 Cancer Res. 41: 2962–2966

  • Whitehouse CJ, Taylor RM, Thistlethwaite A, Zhang H, Karimi-Busheri F, Lasko DD, Weinfeld M, Caldecott KW . 2001 Cell 104: 107–117

  • Zhou W, Sokoll LJ, Bruzek DJ, Zhang L, Velculescu VE, Goldin SB, Hruban RH, Kern SE, Hamilton SR, Chan DW, Vogelstein B, Kinzler KW . 1998 Cancer Epidemiol. Biomarkers Prev. 7: 109–112

Download references

Acknowledgements

We are grateful to George Elia and members of the Cancer Research UK Histopathology Laboratory for technical assistance; Nick Hathaway, Steve Keirnan and Susan van Noorden of the Department of Histopathology, Hammersmith Hospital for help with tissue sectioning. Work was supported by grants from Cancer Research UK, Hammer Cancer, Hammersmith Hospitals Special Trustees, as well as (to A Scarpa) Associazione Italiana Ricerca Cancro, Milan, Italy and Ministero Università Cofin MM06158571, Rome, Italy.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Nicholas R Lemoine.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Crnogorac-Jurcevic, T., Efthimiou, E., Nielsen, T. et al. Expression profiling of microdissected pancreatic adenocarcinomas. Oncogene 21, 4587–4594 (2002). https://doi.org/10.1038/sj.onc.1205570

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1205570

Keywords

This article is cited by

Search

Quick links