We would like to do more research on the in vivo development of ER-positive breast cancer in mice. So we are interested in either a transgenic mouse strain that develops this cancer type or alternatively a carcinogen that specifically induces ER-positive breast cancer. Any suggestions welcome.
Dear Dr Guericke,
I dont know any specific model, but I think you could try to transplant a xenograft of MCF7 cells in nude mice.
Good luck! Carolina Panis
Most likely, there is none that closely resembles the most common ER-positive human cancers. This subtype takes years to come to a clinically significant level. Any ER-postive model that results in palpable tumors within weeks or months can be considered not to represent the human situation.
The transplantable MXT mouse mammary tumor that is synegenic to B6D2F1 mice is ER and PR positive.
The best and most commonly estrogen DEPENDENT model is an MCF7 xenograft into female nude mice supplemented with estradiol. Variations of this model have been very clinically informative leading to the development of estrogen receptor modulators (tamoxifen) and aromatase inhibitors. As mentioned above, it is not a good model for cancer initiation. Another drawback is this model requires the supplementation of estradiol to take and grow. We graft orthotopically into the mammary fat pad to best modl the tumor microenvironment.
Dear Dr. Nobert!
Yeah! I am also agree with Nelson and Paril. Its very difficult to establish ER+ breast cancer Mouse model neither by carcinogen nor by transgenics . in case of ER+ state you hardly detect clinical significant palpable tumors because its not aggressive and invasive. I feel its better to make orthrotropic xenograft model by injecting the MCF-7 into mammary pads of mice and supplementation of estradiol is recommended to induce the tumor in the same mice.
No mouse transgenic models are truly representative of human ER+ tumors, especially luminal A tumors. The p53 +/- model developed by Dan Medina at Baylor comes close. Also, mice with mammary gland expression of constitutively active AKT (myrAKT) develop ER+ tumors upon DMBA treatment ( Carcinogenesis (2006) 28 (3): 584-594. doi: 10.1093/carcin/bgl190) . To my knowledge, this is the closest model to human tumors (because PI3K activating mutations are reasonably common in human ER+ cancers, although activating mutations of AKT are less common), however it is quite time-consuming. There are some transplantable mouse models like MXT and E0771 that are ER+, though in our hands E0771 is tamoxifen-resistant. Most investigators use xenografts of MCF7 for luminal A and T47D for luminal B tumors. These can grow in intact mice or in ovariectomized mice supplemented with postmenopausal levels of estrogen in subcutaneous capsules. Patient-derived xenografts are very difficult to establish from ER+ tumors. I know of a group that has a few in the UK, but they are not widely available.
For the best mouse model, you can go for Female Balb/c athymic nude mice, transplanted with ER+ xenografts or subcutaneous injection of MCF-7 cells. For optimum and balanced growth in all animals, you need to do overiectomy and should suppliment Estradiol. You can use 30days or 60 days controlled release Estradiol pellets (depending on the duration of your study) and can implant subcutaneously. Use mammary fat pad for subcutaneous injection/xenograft transplantation as the fat pad will provide a tumor micro environment. Controlled release pellets can be transplanted behind the neck, so that mice cannot scratch over there.
Hope this would help your question... Best of luck for your research.
Hello Nass,
yes i agree with all above responses,just i would like to add about MATRIGEL(BD) for better take up & growth of tumors.
Inject MCF7:matrigel(1:1) 0.2 ml subcutaneously after recovery frm overiectomy of NUDE Females.Prior to that just implant 60 days estradiol slow release pellet.
Good luck...
milind
Humbly, I think you can find useful information in this review, in case you haven't yet read it
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3263010/
US-20120222139 A1 talks about “HuMAb-Mouse” is a strain of transgenic mice which harbor the entire human immunoglobin (Ig) loci and thus can be used to produce fully human monoclonal antibodies such as monoclonal anti-mitotic network gene antibodies. Referencing another patent U.S. Pat. No. 6,111,166
To add to the above comments - see e.g. Lucio Miele's good comment above about transgenic and xenograft models. It's important to know the limitations of the model you are using, and perhaps use two different models. For instance, MCF7 cells were originally derived from a breast cancer metastasis (pleural effusion) and have been in culture for decades.
see this article http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3263010/
Thank you very much for all these answers. I understood that most of you favour xenografts, however I agree that most of the cells used, such as MCF-7 have lived in culture for many years now, which was the reason to look for a mouse model with spontanous breast cancer.
Again, thank you very much
Hi, we recently established MCF-7 xenografts to study role of our TF in ER+ tumors. As Dr. Lucio mentioned besides with some limitations it is widely used model now. We injected 1 million cells in the presence of estradiol orthotopically and around 8-12 weeks of time the tumors reached end point of 1.5 cm. Hope this helps as well
Please go through
http://www.epa.gov/endo/pubs/aromatase_fs.pdf
for in vitro aromatase assay for more precise result
BALB-neuT will also be HER2 positive though, so it depends on the receptor status you wish to have for your studies.
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