Question

Directions: You have been studying various oncogenes and tumor suppressor genes in tumor cell lines in vitro, but would now like to address certain questions in mouse models in vivo. For each of the questions below, briefly describe the type of mouse model you would use.

• For xenograft/allograft experiments, briefly describe the type of cell lines you might use and the experimental end points you would be looking at.
• For GEMs, briefly describe the type of mouse you would make (you don’t need to go into details about how the mouse is generated), and the experimental end points you would be looking at.

Note: there is no single right answer. However, try to select the model that would be most straight-forward way to initially address your question.

Question: Oncogenic mutations of the (hypothetical) PRO gene are present in many tumor types, and are associated with high rates of tumor cell proliferation. Several drug companies are therefore trying to develop agents that specifically inhibit the mutant PRO gene product without affecting the normal protein. One company has approached you to assist with in vivo studies to test the efficacy of this agent and its specificity for tumors with PRO mutations. What type of mouse model would you propose to use?

Answer 1

For xenocraft model specially in vitro culture we used when we want to examine the certain drugs or molecules to determine the anti-cancer properties of certain drugs or molecules, This technique is the primary but considered as "gold standard" in cancer research you would like to use lung cancer cell lines or ovarian cancer cell lines. In this procedure, cells are taken from a cancer patient and graft or transplants to the suitable mouse model for further verification of anti-cancer drugs. (this is known as in vivo testing of drug). You may use lung cancer cell lines or ovarian cancer cell line through this procedure. In case of allograft, which happens to be between different people where one organ or part of an organ can be transplanted to the another person.

GEMs or genetically engineered models (mice) are being used in cancer research due to advancement and variability and a number of over-expressed, knockout (complete of conditional, deficient of one exon) or transgenic mice models are available for understanding of the disease and also for development of effective medicines. For example nude mice are the good choice in cancer research as they are lacking of thymus due to certain mutation.

For oncogenic mutation of pro-genes , p53 (tumor suppressor gene) overexpressed or Knock out mice can be used for the drug evaluation, more more detail please go through following citations

1. Pylayeva-Gupta, Y., Grabocka, E., & Bar-Sagi, D. (2011). RAS oncogenes: weaving a tumorigenic web. Nature Reviews Cancer, 11(11), 761-774.

2. Lane, D. P., & Benchimol, S. (1990). p53: oncogene or anti-oncogene. Genes Dev, 4(1), 1-8.

3. Carroll, A. G., Voeller, H. J., Sugars, L., & Gelmann, E. P. (1993). p53 oncogene mutations in three human prostate cancer cell lines. The Prostate, 23(2), 123-134.