Guardian

Yesterday we talked about how cancer is caused by non-lethal genetic mutation. We mentioned the six particularly nasty features that cancer cells acquire when they undergo genetic mutation: autonomous growth, insensitivity to growth inhibitory signals, evasion of apoptosis, limitless replication, sustained angiogenesis, and invasion/metastasis. And we talked about the four types of genes that commonly get mutated in cancer: genes that promote growth (proto-oncogenes), genes that inhibit growth (tumor-suppressor genes), genes that regulate apoptosis, and genes involved in DNA repair. Now let’s talk about three specific genes that are commonly mutated in cancer.

1. RAS gene
This gene encodes a signal transduction protein (the RAS protein) that takes the signal from a growth receptor and transduces it to the cell nucleus so that the cell can proliferate. It’s a normal protein, just like all the others in this list; we all have it in all of our cells. It’s a proto-oncogene – meaning it’s necessary for normal cell growth and proliferation. But when it gets mutated in such a way that it’s always on (at this point it’s called an oncogene), then it’s always transducing signals, and the cell is always proliferating…which is great if you’re a cancer cell because then you’re growing like crazy. The RAS gene is mutated in up to 30% of all human tumors. It’s particularly commonly mutated in colon and pancreatic cancer.

2. Retinoblastoma gene
This gene encodes a protein that stops cells at the G1 checkpoint in the cell cycle. This is important – the cell needs to stop and see if all the DNA is okay before it progresses to mitosis. It is like a little set of brakes for the cell cycle; it falls into the tumor-suppressor gene category. If you mess up this gene (actually, you have to mess up both copies in order to get cancer), you remove the brakes from the cell cycle, and the cell proliferates like crazy. The RB gene is mutated in most cancers!

3. p53 gene
This gene is nicknamed “guardian of the genome” (kinda like the guy in the image above). It does a couple very important things. If a cell’s DNA gets damaged, the p53 protein causes a pause in the cell cycle (via RB!) so the DNA can get repaired. If the DNA gets repaired, fine. If the damage is irreparable, however, p53 tells the cell to kill itself (by apoptosis). Most human tumors have p53 mutations! It’s so critical to the health of the cell’s DNA – you can see why you’d almost have to have a mutation in it in order to get cancer.