In this lecture, we looked at ways you use immunity to defend yourself from yourself. Many people think that cancer is a disease that attacks different parts of the body. I would like you to shift your thinking and view cancer as anti development. Previous discussions on how NK and CTL cells attack rogue cell, that term included both viral infected and malignant cells. I define these cells as those that were not cooperating for the greater good of the body. Just as there are a great many viruses that can infect cells and turn them to the dark side, so there are many ways for your own cells to turn to the dark side, and use your resources for their own nefarious purposes. Cancer is not a disease, but rather a group of related conditions where cells stop functioning as part of a larger organism. Such cells ignore or subvert the very complex and interrelated signals that allow cells to develop into different tissues, cooperate, attached to each other, divide only when more of them are needed, and adapt their specific behaviors to the overall function of a multi-cellular body. This is a giant microbe representation of a happy, healthy cell. What does the cell do? It receives signals from the cell surrounding it and from the compounds in the interstitial fluid. It performs a function. It might be a muscle cell, it might be a nerve cell, a gut cell, or even a hematopoietic stem cell. In any event, it has an assigned location in the body. It may touch or even attach to specific cells around it. It will receive signals from these cells. Those signals will tell it when to act and when not to act. It will send signals to tell other cells when to act and not to act. When we look at cancer, we are looking at the breakdown in the processes that allow cells to produce a functioning organism. Think of a city as an analogy for your body. You can see the complete breakdown of sewage disposal, grocery delivery, or public schools might bring the city to a halt. Breakdown in communications can have similar general effects in coordinating functions. We've probably all experienced consternation when a business could not access our credit card accounts. What if all the cell phone towers in your city suddenly went out? It's easy to see that a complex entity relies on both information and mass transfer, and when someone defrauds a bank, burns down houses, steal food, drives on the wrong side of the road and run stop lights well, you want to put a stop to that. When cells go cancerous, it is if they decide to stop behaving like good citizens and behave more like a bacterial infection. So how does this happen? With a healthy cell, one of the first things that happens on the way to cancer is that cells begin to divide too often, too rapidly, allowing mistakes to slip through and lose the controls that only produce cells that are needed. This can happen if a cell mutates an oncogene or a cancer-causing gene. Now seriously, do you think you are cursed with genes whose purpose is to give you cancer? Oncogenes are genes that you need to trigger cell division. When they function normally, they're called proto-oncogene or cellular oncogene or something like see C-onc for short. But they can trigger malignancy if they are overexpressed or flat out mutated into something abnormal, this can trigger an abnormal growth. Notice, this is a disorganized mass of cells, quite different from the surrounding tissue. This is the opposite of the kind of organization needed to build a functioning you. There are even viruses that use their own versions of oncogenes to subvert a cell. DNA and retroviruses that integrate into the host genome often code for viral oncogenes and those are called v-oncs. Their own version of these genes as part of a strategy to boost the growth of infected cells. This is how some viral infections may lead to cancer. This was first observed in chickens by Peyton Rous. The Rous sarcoma viruses causes solid tumors in poultry. Scientists have identified a number of viruses in humans, including HPV, the human papillomavirus, which cause cervical cancer. We have recently developed vaccines through this discussed in the vaccine lecture. Cells can also mutate tumor suppressor genes. These code for signals, and there are receptors that tell cells not to divide. They were first identified when mutated versions produce tumors in mice. Whereas up-regulating oncogenesis is like having your cars' accelerator stuck, this problem is more analogous to having your break lines cut. Either problem may send you barreling down the highway, or in the case of cells dividing wildly. This is a similar mistake, but different in that the signal is blocked. You don't make too much of it. You stop making the receptor for it, or somehow block the internal pathway that's supposed to transmit it. Now, this refers to the formation of tumors in the retina of the eye. For example, the RB gene produces a protein RB1 that binds to a number of proteins that regulate the cell cycle. It complexes with a variety of other proteins including cyclins and histones, and prevents the synthesis of genes required for a cell to leave G1 and enter S. This is a gene to ensure that a cell does not begin the division process until the body needs another cell, and it has acquired the resources to produce it. One additional malfunction involves blocking apoptosis or programmed cell death. Genes involved in apoptosis are sometimes categorized as tumor suppressor genes, but the specific function is worth considering separately. You probably do start to get cancer all the time. If you're producing a number of cells with an assortment of random mutations, sometimes individual cells can fix the problem. But if the damage cell cannot fix the problem, cells have internal control that cause them to undergo apoptosis, and if they escape that, there is often an immune cell monitor that reinforces the message. One of the principal functions of NK cells and CTLs is to rid you of these early cancers. Most incipient cancer cells wind up like this. But if the cell mutates the genes for the very signals that allow this, then it will ignore the instructions to fall on its sword and die and continue to produce more and more damaged and mutating copies of itself. So you can up-regulate the apoptosis breaks. That is in some free cancers, you undo the production or receipt of something called BCL2, which prevents apoptosis. Too much and you will have trouble getting rid of damaged cells. This is what the Epstein-Barr virus does. Many people have heard of this virus because it causes infectious mononucleosis and that attacks B cells. It also causes various cancers, including Burkitt lymphoma. Epstein-Barr virus or EBV has a gene very similar to the one for BCL2, and this can block attacks by both NK cells and cytotoxic T cells. All of these set the stage for the evolution of normal cells into dangerous ones. The more times a cell divides, the more opportunities it has to make a mistake in its DNA. The more random errors the DNA accumulates, the more likely the cell is to accumulate a hit that leads to further problems in regulation and control. You will wind up making more cells than you need. That in itself is not that big a deal, but it's the thing that gives you a benign skin mole or an annoying skin tag or a polyp. So simply having your cells divide excessively is not likely to kill you. The series of events that produces a malignant cell that has divided too often and evaded all instruction to try to rein it in, that will produce a hypoplasia, but for cancer to actually kill you, it needs to learn how to do a few more things, which we will look at in the next clip.