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:

Murine pancreatic tumor cell line TD2 bears the characteristic pattern of genetic changes with two independently amplified gene loci

Abstract

TGFα/p53+/− transgenic mice represent a genetically engineered mouse model for pancreatic adenocarcinoma. The tumors develop a characteristic pattern of secondary genetic changes. From one of these tumors, the permanent cell line TD2 was established. Here, we describe in detail the genetic changes by molecular–cytogenetic techniques. The original tumor-specific CGH profile has been retained unchanged. The most characteristic aberration pattern bears chromosome 11. Egfr, localized on proximal chromosome 11, is amplified two to three times and leads to an easily identifiable, stable marker chromosome with a large amplification unit, which is present in each metaphase. The wild-type p53 gene on distal chromosome 11 is lost. The p16Ink4a locus on chromosome 4 is hypermethylated. For c-Myc a 15-fold amplification, present in a 1.65 Mb amplification unit, is detected on chromosome 15. Transition between presence in the form of several double minutes, DMs, or a single homogeneously staining region, HSR, was observed for c-Myc. Molecular–cytogenetic analysis of both amplification units show that Egfr amplification and c-Myc amplification represent two alternative modes by which genes get amplified in tumor cells. The expression level of the respective genes was proven by Northern blot analysis. The cell line TD2 represents a valuable in vitro model for pancreatic adenocarcinoma.

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

Access options

Buy this article

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

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7

Similar content being viewed by others

References

  • Bardeesy N, Morgan J, Sinha M, Signoretti S, Srivastava S, Loda M, Merlino G and DePinho RA . (2002). Mol.Cell. Biol., 22, 635–643.

  • Bardeesy N, Sharpless NE, DePinho RA and Merlino G . (2001). Semin. Cancer Biol., 11, 201–218.

  • Caldas C, Hahn SA, da Costa LT, Redston MS, Schutte M, Seymour AB, Weinstein CL, Hruban RH, Yeo CJ and Kern SE . (1994). Nat. Genet., 8, 27–32.

  • Curtis LJ, Yong L, Gerbault-Sereau M, Kuick R, Dutrillaux A-M, Goubin G, Fawcett J, Cram S, Dutrillaux B, Hanash S and Muleris M . (1998). Genomics, 53, 42–55.

  • Gilmore TD . (1999). Oncogene, 18, 6842–6844.

  • Greten FR, Weber CK, Greten TF, Schneider G, Wagner M, Adler G and Schmid RM . (2002). Gastroenterology, 123, 2052–2063.

  • Hajkova P, EI Maarri O, Engemann S, Oswald J, Olek A and Walter J . (2002). Methods Mol. Biol., 200, 143–154.

  • Hellman A, Zlotorynski E, Scherer SW, Cheung J, Vincent JB, Smith DI, Trakhtenbrot L and Kerem B . (2002). Cancer Cell, 1, 89–97.

  • Hruban RH, Goggins M, Parsons J and Kern SE . (2000). Clin. Cancer Res., 6, 2969–2972.

  • Kallioniemi A, Kallioniemi OP, Sudar D, Rutovitz D, Gray JW, Waldman F and Pinkel D . (1992). Science, 258, 818–821.

  • Ma C, Martin S, Trask B and Hamlin JL . (1993). Genes Dev., 7, 605–620.

  • Maurer BJ, Lai E, Hamkalo BA, Hood L and Attardi G . (1987). Nature, 327, 434–437.

  • Patel AC, Anna CH, Foley JF, Stockton PS, Tyson FL, Barrett JC and Devereux TR . (2000). Carcinogenesis, 21, 1691–1700.

  • Paulson TG, Almasan A, Brody LL and Wahl GM . (1998). Mol. Cell. Biol., 18, 3089–3100.

  • Sandgren EP, Luetteke NC, Palmiter RD, Brinster RL and Lee DC . (1990). Cell, 61, 1121–1135.

  • Sandgren EP, Quaife CJ, Paulovich AG, Palmiter RD and Brinster RL . (1991). Proc. Natl. Acad. Sci. USA, 88, 93–97.

  • Schwab M . (1999). Semin. Cancer Biol., 9, 319–325.

  • Steinle AU, Weidenbach H, Wagner M, Adler G and Schmid RM . (1999). Gastroenterology, 116, 420–430.

  • Toledo F, Le Roscouet D, Buttin G and Debatisse M . (1992). EMBO J., 11, 2665–2673.

  • Wagner M, Greten FR, Weber CK, Koschnick S, Mattfeldt T, Deppert W, Kern H, Adler G and Schmid RM . (2001). Genes Dev., 15, 286–293.

  • Wahl GM . (1989). Cancer Res., 49, 1333–1340.

  • Wang W, Abbruzzese JL, Evans DB, Larry L, Cleary KR and Chiao PJ . (1999). Clin. Cancer Res., 5, 119–127.

  • Weaver ZA, McCormack SJ, Liyanage M, du MS, Coleman A, Schrock E, Dickson RB and Ried T . (1999). Genes Chromosom. Cancer, 25, 251–260.

  • Wu Y, Renard CA, Apiou F, Huerre M, Tiollais P, Dutrillaux B and Buendia MA . (2002). Oncogene, 21, 1518–1526.

Download references

Acknowledgements

We thank Antje Kollak, Alexandra Kilian and Beate Knobl for excellent technical assistance. This work was supported by grants from the Deutsche Forschungsgemeinschaft SFB 518 (Teilprojekt B6) and IZKF Ulm (Teilprojekt C4) to RMS.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Roland M Schmid.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schreiner, B., Greten, F., Baur, D. et al. Murine pancreatic tumor cell line TD2 bears the characteristic pattern of genetic changes with two independently amplified gene loci. Oncogene 22, 6802–6809 (2003). https://doi.org/10.1038/sj.onc.1206836

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1206836

Keywords

This article is cited by

Search

Quick links