Mammary glands reconstituted with Neu/ErbB2 transformed HC11 cells provide a novel orthotopic tumor model for testing anti-cancer agents - PubMed (original) (raw)
Comparative Study
. 2001 Sep 6;20(39):5459-65.
doi: 10.1038/sj.onc.1204709.
Affiliations
- PMID: 11571643
- DOI: 10.1038/sj.onc.1204709
Comparative Study
Mammary glands reconstituted with Neu/ErbB2 transformed HC11 cells provide a novel orthotopic tumor model for testing anti-cancer agents
R Brandt et al. Oncogene. 2001.
Abstract
The ErbB2 receptor tyrosine kinase (RTK) has been intensely pursued as a cancer therapy target due to its association with breast cancer. In this study we used the HC11 mammary epithelial cell line to develop an orthotopic, ErbB2-driven tumor model for testing efficacy of anti-cancer compounds. HC11 cells were infected with a retrovirus encoding oncogenic NeuT, the rat homolog of ErbB2. Drug-selected populations were introduced into mammary fat pads of Balb/c syngeneic mice cleared of host tissue. The majority of glands injected with HC11-NeuT cells developed mammary tumors which appeared after a 3-4 week latency period and grew rapidly. HC11 cells infected with the control retrovirus showed no tumor growth after injection. Tumor-bearing mice were used to compare the in vivo efficacy of two anti-cancer agents: PKI166, a kinase inhibitor selective for EGF receptor and ErbB2, and Taxol, a microtubule assembly blocker. PKI166 inhibited NeuT-induced mammary tumor growth in a dose-dependent manner and at a dose below the maximum tolerated dose (MTD) was significantly more inhibitory than Taxol at its MTD (57% vs. 25% tumor regression). Importantly, there was a dose-dependent decrease in the phosphotyrosine content of NeuT isolated from PKI166-treated, tumor-bearing mice, providing a mechanistic link between kinase inhibition and its anti-tumor activity. Thus, implantation of genetically manipulated HC11 cells into mammary glands appears to be an excellent model for studying effects of anti-cancer agents in an orthotopic site.
Similar articles
- Effects of epithelial growth factor receptor (EGFR) kinase inhibitors on genetically reconstituted mouse mammary glands.
Roth DR, Roman D, Cozens R, Brandt R, Seewald W, Greiner B, Wenger F, Mamom T, Germann PG. Roth DR, et al. Exp Toxicol Pathol. 2003 Nov;55(4):237-45. doi: 10.1078/0940-2993-00329. Exp Toxicol Pathol. 2003. PMID: 14703768 - AEE788: a dual family epidermal growth factor receptor/ErbB2 and vascular endothelial growth factor receptor tyrosine kinase inhibitor with antitumor and antiangiogenic activity.
Traxler P, Allegrini PR, Brandt R, Brueggen J, Cozens R, Fabbro D, Grosios K, Lane HA, McSheehy P, Mestan J, Meyer T, Tang C, Wartmann M, Wood J, Caravatti G. Traxler P, et al. Cancer Res. 2004 Jul 15;64(14):4931-41. doi: 10.1158/0008-5472.CAN-03-3681. Cancer Res. 2004. PMID: 15256466 - Elevated expression of DecR1 impairs ErbB2/Neu-induced mammary tumor development.
Ursini-Siegel J, Rajput AB, Lu H, Sanguin-Gendreau V, Zuo D, Papavasiliou V, Lavoie C, Turpin J, Cianflone K, Huntsman DG, Muller WJ. Ursini-Siegel J, et al. Mol Cell Biol. 2007 Sep;27(18):6361-71. doi: 10.1128/MCB.00686-07. Epub 2007 Jul 16. Mol Cell Biol. 2007. PMID: 17636013 Free PMC article. - Unlimited division potential of precancerous mouse mammary cells after spontaneous or carcinogen-induced transformation.
Daniel CW, Aidells BD, Medina D, Faulkin LJ Jr. Daniel CW, et al. Fed Proc. 1975 Jan;34(1):64-7. Fed Proc. 1975. PMID: 162797 Review. - ErbB2 transgenic mice: a tool for investigation of the immune prevention and treatment of mammary carcinomas.
Quaglino E, Mastini C, Forni G, Cavallo F. Quaglino E, et al. Curr Protoc Immunol. 2008 Aug;Chapter 20:Unit 20.9.1-20.9-10. doi: 10.1002/0471142735.im2009s82. Curr Protoc Immunol. 2008. PMID: 18729063 Review.
Cited by
- Global Down-regulation of Gene Expression Induced by Mouse Mammary Tumor Virus (MMTV) in Normal Mammary Epithelial Cells.
Ahmad W, Panicker NG, Akhlaq S, Gull B, Baby J, Khader TA, Rizvi TA, Mustafa F. Ahmad W, et al. Viruses. 2023 May 2;15(5):1110. doi: 10.3390/v15051110. Viruses. 2023. PMID: 37243196 Free PMC article. - Genomic Instability Is an Early Event in Aluminium-Induced Tumorigenesis.
Mandriota SJ, Tenan M, Nicolle A, Jankowska JD, Ferrari P, Tille JC, Durin MA, Green CM, Tabruyn S, Moralli D, Sappino AP. Mandriota SJ, et al. Int J Mol Sci. 2020 Dec 7;21(23):9332. doi: 10.3390/ijms21239332. Int J Mol Sci. 2020. PMID: 33297592 Free PMC article. - MMP-9 inhibition promotes anti-tumor immunity through disruption of biochemical and physical barriers to T-cell trafficking to tumors.
Juric V, O'Sullivan C, Stefanutti E, Kovalenko M, Greenstein A, Barry-Hamilton V, Mikaelian I, Degenhardt J, Yue P, Smith V, Mikels-Vigdal A. Juric V, et al. PLoS One. 2018 Nov 30;13(11):e0207255. doi: 10.1371/journal.pone.0207255. eCollection 2018. PLoS One. 2018. PMID: 30500835 Free PMC article. - Anticancer Properties of Halogenated Pyrrolo[3,2-d]pyrimidines with Decreased Toxicity via N5 Substitution.
Cawrse BM, Lapidus RS, Cooper B, Choi EY, Seley-Radtke KL. Cawrse BM, et al. ChemMedChem. 2018 Jan 22;13(2):178-185. doi: 10.1002/cmdc.201700641. Epub 2017 Dec 18. ChemMedChem. 2018. PMID: 29193845 Free PMC article. - Molecular Mechanisms of Trastuzumab-Based Treatment in HER2-Overexpressing Breast Cancer.
Nahta R. Nahta R. ISRN Oncol. 2012;2012:428062. doi: 10.5402/2012/428062. Epub 2012 Nov 22. ISRN Oncol. 2012. PMID: 23227361 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials
Miscellaneous