Table 1.
Genetically engineered mouse models that develop ER+ breast cancer
| A. Models developing ER+ mammary cancer from direct over-expression of ERα | |||||||
|---|---|---|---|---|---|---|---|
| Published Nomenclature |
Genetic Nomenclature |
Background Strain |
Age range of mice demonstrating cancer development (months) |
Percentage of mice with mammary cancers within this age range |
Percentage of mammary cancers designated ER+ |
Parity required for tumor development |
Refs |
| tTA/TAg/ER-α | Tet-op-Esr1MMTV-tTA/tet-op-SV40-TAg | C57Bl/6 | 10–12 | 37% | 100% | No | Tilli MT, Frech MS, Steed ME, Hruska KS, Johnson MD, Flaws JA & Furth PA 2003 Introduction of estrogen receptor-alpha into the tTA/TAg conditional mouse model precipitates the development of estrogen-responsive mammary adenocarcinoma. Am J Pathol 163 1713–1719. |
| CERM (Conditional Estrogen Receptor alpha in Mammary tissue) | Tet-op-Esr1MMTV-rtTA | C57Bl/6 | 10–12 | 3–5% | 50% | No | Miermont AM 2012 Association of Over-Expressed Estrogen Receptor Alpha with Development of Tamoxifen Resistant Hyperplasia and Adenocarcinomas in Genetically Engineered Mice. Anatomy & Physiology
02. Miermont AM, Parrish AR & Furth PA 2010 Role of ERalpha in the differential response of Stat5a loss in susceptibility to mammary preneoplasia and DMBA-induced carcinogenesis. Carcinogenesis 31 1124–1131. Frech MS, Halama ED, Tilli MT, Singh B, Gunther EJ, Chodosh LA, Flaws JA & Furth PA 2005 Deregulated estrogen receptor alpha expression in mammary epithelial cells of transgenic mice results in the development of ductal carcinoma in situ. Cancer Res 65 681–685. |
| AIB1Δ3/CERM | Tet-op-Esr1MMTV-tTA/tet-op- AIB1Δ3 | C57Bl/6 | 19–26 | 7% | 50% | No | Nakles RE, Shiffert MT, Diaz-Cruz ES, Cabrera MC, Alotaiby M, Miermont AM, Riegel AT & Furth PA 2011 Altered AIB1 or AIB1Delta3 expression impacts ERalpha effects on mammary gland stromal and epithelial content. Mol Endocrinol 25 549–563. |
| Brca1f/f;MMTV-Cre/p53+/−/CERM | Tet-op-Esr1MMTV-rtTA/Brca1 f11/f11/MMTV-Cre/p53+/− | C57Bl/6 | 9–16 | 100% | 50% | No | Jones LP, Assefnia S, Chandrasekharan S, et al. 2007 Identification of conserved gene expression features between murine mammary carcinoma models and human breast tumors. Genome Biol 8 R76. |
| B. Models developing ER+ mammary cancer as a result of genetic alterations of molecules impacting estrogen signaling | |||||||
|---|---|---|---|---|---|---|---|
| Published Nomenclature |
Genetic Nomenclature |
Backgroun d Strain |
Age range of mice demonstrating cancer development (months) |
Percentage of mice with mammary cancers within this age range |
Percentage of mammary cancers designated ER+ |
Parity required for tumor development |
Refs |
| MMTV-cyclinD1 | MMTV-Ccdn1 | C57Bl/6 | 12 | 5% | 100% | No | Miermont AM 2012 Association of Over-Expressed Estrogen Receptor Alpha with Development of Tamoxifen Resistant Hyperplasia and Adenocarcinomas in Genetically Engineered Mice. Anatomy & Physiology
02. Wang TC, Cardiff RD, Zukerberg L, Lees E, Arnold A & Schmidt EV 1994 Mammary hyperplasia and carcinoma in MMTV-cyclin D1 transgenic mice. Nature 369 669–671. |
| MMTV-cyclinD1 | MMTV-Ccdn1 | FVB | 20–23 | 47.5% | 37.5% | Yes | Lin DI, Lessie MD, Gladden AB, Bassing CH, Wagner KU & Diehl JA 2008 Disruption of cyclin D1 nuclear export and proteolysis accelerates mammary carcinogenesis. Oncogene 27 1231–1242. |
| MMTV-D1T286A | MMTV-Ccdn1T286A | FVB | 16–20 | 51% | 50% | Yes | Lin DI, Lessie MD, Gladden AB, Bassing CH, Wagner KU & Diehl JA 2008 Disruption of cyclin D1 nuclear export and proteolysis accelerates mammary carcinogenesis. Oncogene 27 1231–1242. |
| NRL-PRL Line 1655-8 |
Lcn2-Prl1655–8 | FVB | 12–21 | 80% | 50% | No | Rose-Hellekant TA, Arendt LM, Schroeder MD, Gilchrist K, Sandgren EP & Schuler LA 2003 Prolactin induces ERalpha-positive and ERalpha-negative mammary cancer in transgenic mice. Oncogene 22 4664–4674. |
| MMTV-Wnt1 | MMTV-Wnt1 | FVB | 3–7 | 80% | 86% | No | Zhang X, Podsypanina K, Huang S, Mohsin SK, Chamness GC, Hatsell S, Cowin P, Schiff R & Li Y 2005 Estrogen receptor positivity in mammary tumors of Wnt-1 transgenic mice is influenced by collaborating oncogenic mutations. Oncogene 24 4220–4231. |
| P53(R270H/+)WAPCre | p53R270H/+/WAP-Cre | 129Sv/C57BL/6 | 7–8 | 87% | 67% | Yes | Wijnhoven SW, Zwart E, Speksnijder EN, Beems RB, Olive KP, Tuveson DA, Jonkers J, Schaap MM, van den Berg J, Jacks T, et al. 2005 Mice expressing a mammary gland-specific R270H mutation in the p53 tumor suppressor gene mimic human breast cancer development. Cancer Res 65 8166–8173. |
| P53fp/fpWAPCrec | p53fp/fpWAPCrec | CB6F1 × C57BL/6 | 8–12.5 | 92% | 40% | No | Lin SC, Lee KF, Nikitin AY, Hilsenbeck SG, Cardiff RD, Li A, Kang KW, Frank SA, Lee WH & Lee EY 2004 Somatic mutation of p53 leads to estrogen receptor alpha-positive and -negative mouse mammary tumors with high frequency of metastasis. Cancer Res 64 3525–3532. |
| p53 null | p53 | BALB/c | 11–12 | 24–55% | 21% | No | Medina D, Kittrell FS, Shepard A, Stephens LC, Jiang C, Lu J, Allred DC, McCarthy M & Ullrich RL 2002 Biological and genetic properties of the p53 null preneoplastic mammary epithelium. Faseb j 16 881–883. |
| Stat1−/− | 129S6/SvEvTac-Stat1tm1Rds | 129S6/SvEv | 18–26 | 62% | 90% | No | Chan SR, Vermi W, Luo J, Lucini L, Rickert C, Fowler AM, Lonardi S, Arthur C, Young LJ, Levy DE, et al. 2012 STAT1-deficient mice spontaneously develop estrogen receptor alpha-positive luminal mammary carcinomas. Breast Cancer Res 14 R16. |
| TGFα×p53+/− | Nrl-TGFαp53+/− | FVB/N | 9–21 | 100% | “most” | No | Rose-Hellekant TA, Schroeder MD, Brockman JL, Zhdankin O, Bolstad R, Chen KS, Gould MN, Schuler LA & Sandgren EP 2007 Estrogen receptor-positive mammary tumorigenesis in TGFalpha transgenic mice progresses with progesterone receptor loss. Oncogene 26 5238–5246. |
| MMTV-AIB1 | MMTV-AIB1 | FVB/N | 12–25 | 76% | 40% | No | Torres-Arzayus MI, Font de Mora J, Yuan J, Vazquez F, Bronson R, Rue M, Sellers WR & Brown M 2004 High tumor incidence and activation of the PI3K/AKT pathway in transgenic mice define AIB1 as an oncogene. Cancer Cell 6 263–274. |
| MMTV-Espl1 | MMTV-Espl1 | C57Bl/6 | 10–11 | 80% | 100% | Yes | Mukherjee M, Ge G, Zhang N, Edwards DG, Sumazin P, Sharan SK, Rao PH, Medina D & Pati D 2013 MMTV-Espl1 transgenic mice develop aneuploid, estrogen receptor alpha (ERalpha)-positive mammary adenocarcinomas. Oncogene. |
| MMTV-Espl1, p53+/− | MMTV-Espl1p53+/− | C57Bl/6 | 10–11 | 100% | 45% | Yes | Mukherjee M, Ge G, Zhang N, Edwards DG, Sumazin P, Sharan SK, Rao PH, Medina D & Pati D 2013 MMTV-Espl1 transgenic mice develop aneuploid, estrogen receptor alpha (ERalpha)-positive mammary adenocarcinomas. Oncogene |
| Pik3caH1047R | R26-Pik3caH1047R/MMTV-CreNLST | FVB | 5–16 | 69% | 96% | Yes | Adams JR, Xu K, Liu JC, Agamez NM, Loch AJ, Wong RG, Wang W, Wright KL, Lane TF, Zacksenhaus E, et al. 2011 Cooperation between Pik3ca and p53 mutations in mouse mammary tumor formation. Cancer Res 71 2706–2717. |
| C. Model developing ER+ mammary cancer as a result of pharmacologic treatment in combination with genetic alterations of molecules impacting estrogen signaling | ||||||||
|---|---|---|---|---|---|---|---|---|
| GEM Model Published Nomenclature |
Genetic Nomenclature |
Background Strain |
Age range of mice demonstrating cancer development (months) |
Percentage of mice with mammary cancers within this age range |
Percentage of mammary cancers designated ER+ |
Pharmacological Inducer |
Parity required for tumor development |
Ref |
| Brca1f11/f11/p53+/−/MMTV-Cre | Brca1f11/f11/p53+/−MMTV-Cre | C57Bl/6 | 10–12 | 100% | 23% | Efatutazone administered at age 4 months | No | Nakles RE, Kallakury BV & Furth PA 2013 The PPARgamma agonist efatutazone increases the spectrum of well-differentiated mammary cancer subtypes initiated by loss of full-length BRCA1 in association with TP53 haploinsufficiency. Am J Pathol 182 1976–1985. |
| D. Model developing ER+ mammary cancer as a result of carcinogen exposure in combination with genetic alterations of molecules impacting estrogen signaling | ||||||||
|---|---|---|---|---|---|---|---|---|
| Published Nomenclature |
Genetic Nomenclature |
Background Strain |
Age range of mice demonstrating cancer development (months) |
Percentage of mice with mammary cancers within this age range |
Percentage of mammary cancers designated ER+ |
Chemical Inducer | Ref | |
| MMTV-myrAkt1 | MMTV-AKT1myr | C57Bl/6 | 6–12 | 40% | 100 | 7,12-dimethylbenz(a)anthracene (DMBA) treatment for 5 weeks beginning at 9 weeks of age | No | Blanco-Aparicio C, Perez-Gallego L, Pequeno B, Leal JF, Renner O & Carnero A 2007 Mice expressing myrAKT1 in the mammary gland develop carcinogen-induced ER-positive mammary tumors that mimic human breast cancer. Carcinogenesis 28 584–594 |
| E. Model developing ER+ mammary cancer as a result of brother-sister matings of nude mice | ||||||
|---|---|---|---|---|---|---|
| Published Nomenclature |
Background Strain |
Age range of mice demonstrating cancer development (months) |
Percentage of mice with mammary cancers within this age range |
Percentage of mammary cancers designated ER+ |
Parity required for tumor development |
Ref |
| Spontaneous Mammary Tumor model | NIH Nude | 3.5–12 | 62% | 100% | Yes | Kumar MJ, Ponvijay KS, Nandhini R, Nagarajan RS, Jose J, Srinivas G, Nagarajan P, Venkatesan R, Kumar K & Singh S 2007 A mouse model for luminal epithelial like ER positive subtype of human breast cancer. BMC Cancer 7 180. |