Skip to main content

Advertisement

SpringerLink
Log in

Syngeneic mouse mammary carcinoma cell lines: Two closely related cell lines with divergent metastatic behavior

  • Published:
Clinical & Experimental Metastasis Aims and scope Submit manuscript

Abstract

Two cell lines, Met-1fvb2 and DB-7fvb2, with different metastatic potential, were derived from mammary carcinomas in FVB/N-Tg(MMTV-PyVmT) and FVB/N-Tg(MMTV-PyVmT Y315F/Y322F) mice, transplanted into syngeneic FVB/N hosts and characterized. The lines maintain a stable morphological and biological phenotype after multiple rounds of in vitro culture and in vivo transplantation. The Met-1fvb2 line derived from a FVB/N-Tg(MMTV-PyVmT) tumor exhibits invasive growth and 100% metastases when transplanted into the females FVB/N mammary fat pad. The DB-7fvb2 line derived from the FVB/N-Tg(MMTV-PyVmT Y315F/Y322F) with a “double base” modification at Y315F/Y322F exhibits more rapid growth when transplanted into the mammary fat pad, but a lower rate of metastasis (17%). The Met1fvb2 cells show high activation of AKT, while DB-7fvb2 cells show very low levels of AKT activation. The DNA content and gene expression levels of both cell lines are stable over multiple generations. Therefore, these two cell lines provide a stable, reproducible resource for the study of metastasis modulators, AKT molecular pathway interactions, and gene target and marker discovery.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. A Jemal RC Tiwari T Murray (2004) ArticleTitleCancer statistics, 2004 CA Cancer J Clin 54 8–29 Occurrence Handle14974761

    PubMed  Google Scholar 

  2. RD Cardiff MR Anver BA Gusterson et al. (2000) ArticleTitleThe mammary pathology of genetically engineered mice: The consensus report and recommendations from the Annapolis meeting Oncogene 19 968–88 Occurrence Handle10.1038/sj.onc.1203277 Occurrence Handle10713680

    Article  PubMed  Google Scholar 

  3. CT Guy RD Cardiff WJ Muller (1992) ArticleTitleInduction of mammary tumors by expression of polyomavirus middle T oncogene: A transgenic mouse model for metastatic disease Mol Cell Biol 12 954–61 Occurrence Handle1312220

    PubMed  Google Scholar 

  4. EY Lin JG Jones P Li et al. (2003) ArticleTitleProgression to malignancy in the polyoma middle T oncoprotein mouse breast cancer model provides a reliable model for human diseases Am J Pathol 163 2113–26 Occurrence Handle14578209

    PubMed  Google Scholar 

  5. JE Maglione D Moghanaki LJ Young et al. (2001) ArticleTitleTransgenic polyoma middle-T mice model premalignant mammary disease Cancer Res 61 8298–305 Occurrence Handle11719463

    PubMed  Google Scholar 

  6. H Baribault M Wilson-Heiner W Muller et al. (1997) ArticleTitleFunctional analysis of mouse keratin 8 in polyoma middle T-induced mammary gland tumours Transgenic Res 6 359–67 Occurrence Handle10.1023/A:1018427215923 Occurrence Handle9423286

    Article  PubMed  Google Scholar 

  7. RA Graham JR Morris EP Cohen et al. (2001) ArticleTitleUp-regulation of MUC1 in mammary tumors generated in a double-transgenic mouse expressing human MUC1 cDNA, under the control of 1.4-kb 5′ MUC1 promoter sequence and the middle T oncogene, expressed from the MMTV promoter Int J Cancer 92 382–7 Occurrence Handle10.1002/ijc.1192 Occurrence Handle11291075

    Article  PubMed  Google Scholar 

  8. Y Li B Welm K Podsypanina et al. (2003) ArticleTitleEvidence that transgenes encoding components of the Wnt signaling pathway preferentially induce mammary cancers from progenitor cells Proc Natl Acad Sci USA 100 15853–8 Occurrence Handle10.1073/pnas.2136825100 Occurrence Handle14668450

    Article  PubMed  Google Scholar 

  9. KA Jessen SY Liu CG Tepper et al. (2004) ArticleTitleMolecular analysis of metastasis in a polyomavirus middle T mouse model: the role of osteopontin Breast Cancer Res 6 R157–R69 Occurrence Handle10.1186/bcr768 Occurrence Handle15084239

    Article  PubMed  Google Scholar 

  10. D Cozma L Lukes J Rouse et al. (2002) ArticleTitleA bioinformatics-based strategy identifies c-Myc and Cdc25A as candidates for the Apmt mammary tumor latency modifiers Genome Res 12 969–75 Occurrence Handle10.1101/gr.210502 Occurrence Handle12045150

    Article  PubMed  Google Scholar 

  11. TM Williams F Medina I Badano et al. (2004) ArticleTitleCaveolin-1 gene disruption promotes mammary tumorigenesis and dramatically enhances lung metastasis in vivo. Role of Cav-1 in cell invasiveness and matrix metalloproteinase (MMP-2/9) secretion J Biol Chem 279 51630–46 Occurrence Handle10.1074/jbc.M409214200 Occurrence Handle15355971

    Article  PubMed  Google Scholar 

  12. GD Basu LB Pathangey TL Tinder et al. (2004) ArticleTitleCyclooxygenase-2 inhibitor induces apoptosis in breast cancer cells in an in vivo model of spontaneous metastatic breast cancer Mol Cancer Res 2 632–42 Occurrence Handle15561779

    PubMed  Google Scholar 

  13. T Le Voyer Z Lu J Babb et al. (2000) ArticleTitleAn epistatic interaction controls the latency of a transgene-induced mammary tumor Mamm Genome 11 883–9 Occurrence Handle10.1007/s003350010163 Occurrence Handle11003704

    Article  PubMed  Google Scholar 

  14. MA Webster JN Hutchinson MJ Rauh et al. (1998) ArticleTitleRequirement for both Shc and phosphatidylinositol 3’ kinase signaling pathways in polyomavirus middle T-mediated mammary tumorigenesis Mol Cell Biol 18 2344–59 Occurrence Handle9528804

    PubMed  Google Scholar 

  15. J Hutchinson J Jin RD Cardiff et al. (2001) ArticleTitleActivation of Akt (protein kinase B) in mammary epithelium provides a critical cell survival signal required for tumor progression Mol Cell Biol 21 2203–12 Occurrence Handle10.1128/MCB.21.6.2203-2212.2001 Occurrence Handle11238953

    Article  PubMed  Google Scholar 

  16. AT Cheung LJ Young PC Chen et al. (1997) ArticleTitleMicrocirculation and metastasis in a new mouse mammary tumor model system Int J Oncol 11 69–77

    Google Scholar 

  17. SL Friedman FJ Roll (1987) ArticleTitleIsolation and culture of hepatic lipocytes, Kupffer cells, and sinusoidal endothelial cells by density gradient centrifugation with Stractan Anal Biochem 161 207–18 Occurrence Handle10.1016/0003-2697(87)90673-7 Occurrence Handle3578783

    Article  PubMed  Google Scholar 

  18. CJ Vlahos WF Matter KY Hui et al. (1994) ArticleTitleA specific inhibitor of phosphatidylinositol 3-kinase, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002) J Biol Chem 269 5241–8

    Google Scholar 

  19. R Namba JE Maglione LJ Young et al. (2004) ArticleTitleMolecular characterization of the transition to malignancy in a genetically engineered mouse-based model of ductal carcinoma in situ Mol Cancer Res 2 453–63 Occurrence Handle15328372

    PubMed  Google Scholar 

  20. C Li WH Wong (2001) ArticleTitleModel-based analysis of oligonucleotide arrays: Expression index computation and outlier detection Proc Natl Acad Sci USA 98 31–6 Occurrence Handle10.1073/pnas.011404098 Occurrence Handle11134512

    Article  PubMed  Google Scholar 

  21. G Hodgson JH Hager S Volik et al. (2001) ArticleTitleGenome scanning with array CGH delineates regional alterations in mouse islet carcinomas Nat Genet 29 459–64 Occurrence Handle11694878

    PubMed  Google Scholar 

  22. JH Hager JG Hodgson J Fridlyand et al. (2004) ArticleTitleOncogene expression and genetic background influence the frequency of DNA copy number abnormalities in mouse pancreatic islet cell carcinomas Cancer Res 64 2406–10 Occurrence Handle15059892

    PubMed  Google Scholar 

  23. A Rosner K Miyoshi E Landesman-Bollag et al. (2002) ArticleTitlePathway pathology: Histological differences between ErbB/Ras and Wnt pathway transgenic mammary tumors Am J Pathol 161 1087–97 Occurrence Handle12213737

    PubMed  Google Scholar 

  24. C Montagna MS Lyu K Hunter et al. (2003) ArticleTitleThe Septin 9 (MSF) gene is amplified and overexpressed in mouse mammary gland adenocarcinomas and human breast cancer cell lines Cancer Res 63 2179–87 Occurrence Handle12727837

    PubMed  Google Scholar 

  25. YP Shi G Mohapatra J Miller et al. (1997) ArticleTitleFISH probes for mouse chromosome identification Genomics 45 42–7 Occurrence Handle10.1006/geno.1997.4904 Occurrence Handle9339359

    Article  PubMed  Google Scholar 

  26. AK Man LJ Young JA Tynan et al. (2003) ArticleTitleEts2-dependent stromal regulation of mouse mammary tumors Mol Cell Biol 23 8614–25 Occurrence Handle10.1128/MCB.23.23.8614-8625.2003 Occurrence Handle14612405

    Article  PubMed  Google Scholar 

  27. RH Weiss D Marshall L Howard et al. (2003) ArticleTitleSuppression of breast cancer growth and angiogenesis by an antisense oligodeoxynucleotide to p21(Waf1/Cip1) Cancer Lett 189 39–48 Occurrence Handle10.1016/S0304-3835(02)00495-0 Occurrence Handle12445676

    Article  PubMed  Google Scholar 

  28. LY Bourguignon Z Gunja-Smith N Iida et al. (1998) ArticleTitleCD44v(3,8–10) is involved in cytoskeleton-mediated tumor cell migration and matrix metalloproteinase (MMP-9) association in metastatic breast cancer cells J Cell Physiol 176 206–15 Occurrence Handle10.1002/(SICI)1097-4652(199807)176:1<206::AID-JCP22>3.0.CO;2-3 Occurrence Handle9618160

    Article  PubMed  Google Scholar 

  29. DH Lau L Xue LJ Young et al. (1999) ArticleTitlePaclitaxel (Taxol): An inhibitor of angiogenesis in a highly vascularized transgenic breast cancer Cancer Biother Radiopharm 14 31–6 Occurrence Handle10850285

    PubMed  Google Scholar 

  30. MA Webster WJ Muller (1994) ArticleTitleMammary tumorigenesis and metastasis in transgenic mice Semin Cancer Biol 5 69–76 Occurrence Handle8186390

    PubMed  Google Scholar 

  31. TH Qiu GV Chandramouli KW Hunter et al. (2004) ArticleTitleGlobal expression profiling identifies signatures of tumor virulence in MMTV-PyMT-transgenic mice: Correlation to human disease Cancer Res 64 5973–81 Occurrence Handle15342376

    PubMed  Google Scholar 

  32. DJ Slamon W Godolphin LA Jones et al. (1989) ArticleTitleStudies of the HER-2/neu proto-oncogene in human breast and ovarian cancer Science 244 707–12 Occurrence Handle2470152

    PubMed  Google Scholar 

  33. SM Dilworth (2002) ArticleTitlePolyoma virus middle T antigen and its role in identifying cancer-related molecules Nat Rev Cancer 2 951–6 Occurrence Handle10.1038/nrc946 Occurrence Handle12459733

    Article  PubMed  Google Scholar 

  34. G Zhang B He GF Weber (2003) ArticleTitleGrowth factor signaling induces metastasis genes in transformed cells: Molecular connection between Akt kinase and osteopontin in breast cancer Mol Cell Biol 23 6507–19 Occurrence Handle10.1128/MCB.23.18.6507-6519.2003 Occurrence Handle12944477

    Article  PubMed  Google Scholar 

  35. Khanna C, Hunter K. Modeling metastasis in vivo. Carcinogenesis 2004.

  36. RS Kerbel (1998) ArticleTitleWhat is the optimal rodent model for anti-tumor drug testing? Cancer Metastasis Rev 17 301–4 Occurrence Handle10.1023/A:1006152915959 Occurrence Handle10352884

    Article  PubMed  Google Scholar 

  37. JE Maglione ET McGoldrick Lj Young et al. (2004) ArticleTitlePolyomavirus middle T-induced mammary intraepithelial neoplasia outgrowths: Single origin, divergent evolution, and multiple outcomes Mol Cancer Ther 3 941–53 Occurrence Handle15299077

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medical Pathology and Laboratory Medicine, UC Davis School of Medicine, 95817, Sacramento, CA, USA

    Alexander D. Borowsky, Ruria Namba, Lawrence J.T. Young, Clifford G. Tepper, Erik T. McGoldrick, Robert D. Cardiff & Jeffrey P. Gregg

  2. Center for Comparative Medicine, UC Davis, 95616, Davis, CA, USA

    Alexander D. Borowsky, Lawrence J.T. Young, Erik T. McGoldrick & Robert D. Cardiff

  3. Laboratory of Population Genetics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, 20892, Bethesda, MD, USA

    Kent W. Hunter

  4. Department of Neurological Surgery, UC San Francisco, 94143, San Francisco, CA, USA

    J. Graeme Hodgson

  5. Department of Biochemistry and Molecular Medicine, UC Davis School of Medicine, 95817, Sacramento, CA, USA

    Clifford G. Tepper

  6. Molecular Oncology Group, McGill University, Royal Victoria Hospital, Montréal, Québec, Canada

    William J. Muller

Authors
  1. Alexander D. Borowsky
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ruria Namba
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lawrence J.T. Young
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kent W. Hunter
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J. Graeme Hodgson
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Clifford G. Tepper
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Erik T. McGoldrick
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. William J. Muller
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Robert D. Cardiff
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Jeffrey P. Gregg
    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

Borowsky, A.D., Namba, R., Young, L.J. et al. Syngeneic mouse mammary carcinoma cell lines: Two closely related cell lines with divergent metastatic behavior. Clin Exp Metastasis 22, 47–59 (2005). https://doi.org/10.1007/s10585-005-2908-5

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10585-005-2908-5

Keywords

Search

Navigation