The Cell Cycle, Oncogenes and Tumor-Suppressor Genes
Lastly, oncogenes and tumor-suppressor genes—what are they? You'll hear researchers use the terms G0 or G2, or say something like, “I have a drug that hits the M-phase,” or, “ I have an S-phase inhibitor.” What does that mean? Well, we divide cell division into phases. These phases are G0; Gap 1; S-phase or DNA synthesis; Gap 2; and M-phase or mitosis. A cell must go through all these phases in order to divide.
There are checkpoints that exist at each phase in the cell division process. At the checkpoint, the cell checks itself over to make sure it’s OK before it moves on to the next phase. If it’s not OK, it can’t go on. The cell does this to protect you from mutations. Think about it: You are making over a billion cells every day in your blood system. As each cell goes through the cell division process there are signals that tell it to proceed. Those are called growth inducers. They tell the cell, “Let’s go. Keep moving.” And then there are other signals that tell the cell to stop. Those are growth inhibitors. So, basically, it’s a process of one, stop and check; two, make sure everything is OK; and, three, let those cells that look OK proceed.
In each cell there is this “go” signal, and then there's this “stop” signal, and both are required for regulating growth. This means that there are two ways that a cell can accelerate its growth. One is by excessive signaling of the growth inducers. If the cell keeps hearing, “Grow, grow, grow,” it will keep growing out of control. But it’s also possible for the stop signal to stop working. And when this occurs, it’s like removing the checkpoints. The cells don’t stop to make sure they are OK and don’t have any mutations. Those things that tell the cell to go are called cyclins. And if the cyclins are mutated, you will have a gene that is telling the cell, “Go, go, go. Don't pay attention to the checkpoint.” We call a gene that can mutate in a way that disrupts how cells are supposed to grow and divide and that has the potential to transform a normal cell into a cancer cell an oncogene.
How does an oncogene do this? Your DNA forms a structure called a chromosome. Your chromosomes carry two copies of every single one of your genes. That's a protective mechanism that you have so that if one of the genes gets hurt the other gene can fill in. Genes can be dominant or recessive. An oncogene is a dominant gene. This means that if it develops a mutation, that mutation is going to get passed on to all new cells. But remember, you have two of every gene. So, even if one of your oncogenes become mutated, the cell will continue to function the way it should because the normal oncogene will continue to make the right proteins the cell needs to keep the cell in check.
Here’s an example: There is a tumor-suppressor gene called cyclin D1. Cyclin D1 is a good thing; it’s the stop signal that normally keeps the cell in check. As I mentioned, your chromosomes carry two copies of every gene, so your chromosomes have two copies of cyclin D1. Let’s say one of the two cyclin D1 genes gets a mutation. This means that each time your cell divides, it passes on one cyclin D1 gene that’s mutated and one cyclin D1 gene that’s not. To get the tumor-suppressor function to stop working completely, both cyclin D1 genes have to become mutated, and it’s rare for both genes to become mutated at the same time. Many of us right now in this room undoubtedly have one cyclin D1 gene that has a mutation and one that is just fine. And that other one will probably never get a mutation. And as long as you have one good one, then the cell is able to inhibit growth.