Examples of experimental models of human cancer and their use. Modelling human cancer in other organisms allows us to observe and monitor the effect of therapies against the cancer before actually administering it to patients. This is best done in animal models as their biology is most similar to humans’. Non-animal, eukaryotic models are still useful for studying oncogenic processes in pathways that are conserved between the model and humans.
Classical transgenic mice use a tissue-specific promoter to drive the expression of an gene. The aim is to express the gene only in a particular tissue, and see if it causes tumours to form. It should also identify driver and passenger mutations. The downfall of this strategy is that oncogenes usually acts to de-differentiate the cell, so that would switch off the promoter that is driving its expression, resulting in a self-inhibitory feedback loop. Classical knockout mice have one or both copies of a gene knocked out in the germline, so all cells have the knockout. This is good for studying sporadic versus familial loss of heterozygosity events, but there is no control over where and when that gene is deactivated.
Inducible systems include the tet on and tet off systems, where tetracycline/doxycyline results in the induction (tet on) or inhibition (tet off) of the transcription of a gene. In tet on, doxycyline binds a transactivator that drives transcription; in its absence, there is no transcription. In tet off, the transactivator binds the locus without doxycycline; in its presence, the transactivator dissociates from the gene.
Cre-lox systems work by recombining DNA across lox sites. Any sequences occurring in between the lox sites are said to be “floxed”, and is removed upon Cre presence.
The ER-Tam system is a switchable system that works on the protein level. Proteins fused with the estrogen recetor (ER) are not functional unless tamoxifen is present. Tamoxifen can be removed to make the protein nonfunctional again.
in vivo models
Mouse models are widely used due to their evolutionary and genetic similarity to humans. Differences do exist, such as telomere length and mutation rate. They can be the recipient of xenografts and their cancers largely resemble human cancers.
Flies and yeast do not get cancer, but instead serve as models for oncogenic pathways. They can be subject to genetic and chemical screens to identify putative driver mutations causing pathway deregulation, and to identify drugs that can combat such mutations.
Cell cultures are generally not useful for monitoring tumours, because tumours are complex organs made of many cell types, and culture conditions usually maximise prolferation. Organoid culture allows growth of organs in 3D from a patient biopsy. This can be subjected to functional assays, drug screens, and genome editing for truly personalised therapy that is specific to the patient. However, this shares a common downfall with cell culture in that there is no contribution from the tumour microenvironment in a culture.
Sharpless, N.E.; DePinho, R.A. 2006. “The mighty mouse: genetically engineered mouse models in cancer drug development.” Nature Reviews Drug Discovery5 (9):741-754.
Vidal, M.; Cagan, R.L. 2006. “Drosophila models for cancer research.” Current Opinion in Genetics & Development16:10-16.
Xu, H.; Tomaszewski, J.M.; McKay, M.J. 2011. “Can corruption of chromosome cohesion create a conduit to cancer?” Nature Reviews Cancer11 (3):199-210.
- Library study as usual 📚
- Chemistry lecture
- Lunch with my bestie
- Chill time on the grass with my childhood friends
- 4 hour Cell Biology lab (so much trouble readjusting the microscope lens but at least we finished!) 🔬😧
- Lazy dinner (instant miso soup and tofu) 🍲🍴
- Shower and now just reading some anatomy notes in bed 🛁
Such a long day and totally drained 😥😪 but feels good to be learning new stuff! ☺
This isthepathogenic fungus Erysiphe graminis, otherwise known as powdery mildew. It infects a plant by extending specialized absorptive cells called haustoria from its hyphae into a host plant’s epidermal cells.
This was my first semester as a grad student, and it was also my first time teaching a class. I was the instructor for cell biology lab and it was a great experience! I want to thank my students for an awesome semester and congratulate them on finishing the lab!
Sorry for the few posts! I’ve been working on manuscripts and my dissertation. I’m a few months away from finishing my PhD at Purdue. I hope you all aren’t missing me too much while I take this social media hiatus.
I was video interviewed for Purdue.
I teach a cell biology lab now.
Research is going well. Next week, I will meet van Mil. My research is heavily based on his dissertation so I’ll likely be star struck.
I play bike polo to keep blood pumping.
I’m back on the dating scene.
I officiated my cousin’s wedding. The picture is of my sis and I. The bolo was my grandpa’s (RIP).
My hairdresser has a blog! Follow her. She is awesome thejennagirl.
Alright back to tumblr hibernation. I will emerge a beautiful butterfly doctorate.