Oncogenes and Tumor Suppressors - Video Tutorials & Practice Problems

Oncogenes and Tumor Suppressors

Hi in this video, I'm gonna be talking about uncle jeans and tumor suppressors. So first I just want to talk about cancer as a whole. So cancer cells have a variety of different properties. And I just want to go over a few of these properties before moving on to talking about the specific mutation and the specific genes that give them these properties. So cancer cells have a variety of mutation and these give them certain properties. So the first is sort of growth without growth signals. So these cell cancer cells aren't being stimulated by growth signals but they're still growing and mutations allow them to do that. They're also insensitive to antigrowth signals. So they may be receiving, you know, stop growing signals from their surrounding environment. But they don't listen to that because they don't need to because mutations have allowed them to ignore it. They also have the ability to evade a popped Asus of cell death. Right? So these these cells obviously aren't dying even though they're being told to. Um So they're just like I'm ignoring that and I'm just gonna grow. Then they also have unlimited replication. So generally cells can't just replicate all the time. That's why we have cell death. But cancer cells obviously they form these large tumors, travels to other sites and form large tumors and in order to do that, they have to undergo so many fast rounds of replication and this is very abnormal. So the mutations allow them to do this. They also have angiogenesis properties which if you remember angiogenesis is the formation of blood vessels. So the tumor cells need blood vessels because they need things like oxygen and nutrients and the tumor. Um But normally those blood vessels wouldn't be there. So tumors have to be able to stimulate the growth of new blood vessels to survive. These cells have the ability to invade and you know, spread or metastasize to other tissues, which is a very unique property that very few cells um have in the body. And then finally they're genetically unstable, meaning that they accumulate mutations at a rapid rate. So when we talk about genes that are mutated, um there's a lot of them and they do. They usually provide the cancer cells one of at least one of these seven properties if not multiple at the same time. So let's talk about the first type of genes. So these are called ankle jeans. And these are mutated genes that become over expressed and support cancer. So, uncle genes when mutated become really highly expressed and the expression of those genes lead to one or more of those seven things we've previously talked about. So um ankle jeans can become ankle jeans through mutations or through gene amplification. So obviously we're talking about being over expressed. So if a gene that is an ankle jean is not necessarily directly mutated but copy multiple times and duplicated. Then you have twice the amount of gene and you get twice the amount of expression and that's over expression as well. We call proto oncogene sort of the normal the not mutated versions but they obviously become anka genes when mutated. So because the uncle genes are being over expressed generally what they cause is self proliferation, survival and tumor development. And so typical uncle genes are things like growth factors which when mutated over express and stimulate a lot of growth. Their receptors that stimulate growth signaling pathways. HGTV binding proteins which we've seen have a ton of responsibilities in the cell for signaling, including approaching kindnesses receptor or non receptor transcription factors. You can imagine of transcription factors are over expressed. Then you're going to be transcribing a bunch of jeans at a very high level and then regulator of the cell cycle apoptosis. Um so all of these pathways you can imagine how if any of these things are over expressed that can lead to one of the seven or multiple of the seven characteristics that we talked about previously and lead to cancer growth. So a big important one is Wrasse. We've talked about rats before mainly in terms of signaling. Remember Wrasse is a G. T. P. S. But it's also an uncle gene. And so when it's mutated we call an uncle gene and it's actually mutated in 20% of human cancers. So 20% of all the human cancers that exists on the world are due to the fact that Wrasse has some kind of mutation. So that's like insane right? Because if grass is over expressed then you have all these other pathways being over expressed. So here we have this picture which you may have seen previously. So we have some type of cancer causing agents and it's causing mutations and DNA will say this is Wrasse. Um this becomes activated through some more additional mutations and can lead to the cancer cell development. Remember ANka genes are going to be over expressed and have high levels or increased levels of activity. Then the the exact opposite of that is going to be tumor suppressors. And these are genes that would mutated result in a loss of activity and lead to cancer. So the activity loss of tumor suppressors suppressors are mutated. So they're lost to the cells that function that they have was lost and that leads to self cooperation survival in tumor development. So an example of this is P 53. We've talked about P 53 before and signaling and it's a transcription factor and it is also a tumor suppressor. So normally P 53 in the cell responds to DNA damage and tell tells the cell, hey, you have DNA damage, you need to repair Well in cancer cells don't want that, right? They want this accumulation of mutations. This accumulation of damage. So what they do is they mutate P 53 so it can't work. So when the the activity of P 53 is lost, those cancer cells now have no way of checking whether their DNA is damaged and so the cell doesn't respond to it leads to more mutations that are accumulated and cells dividing with mutations and you can very easily see how that leads to tumors. Another one that we talked about is retinoblastoma. This is also a tumor suppressor that regulates the cell cycle, and this is actually an interesting one because retinoblastoma can occasionally be mutated and when it is, that mutated form can be inherited if it's actually in the germ cells. So here's an example. We get some type of DNA damage. Um and it affects P 53 when P 53 is not here and that's going to block the apoptosis pathway and death of cells. It's also going to block cell cycle or less DNA repair and cell cycle restart. So none of this is going to happen. So you can imagine that even if there's D. N. A damage, the cell is just gonna go and divide and it's gonna have no idea. So it can't repair that, which is obviously bad for us. But great for if you're so with that, let's now turn the page

Tumor suppressors are mutated genes that results in higher amounts of gene activity.

• A. True
• B. False

Which of the following properties is not one given to cancer by gene mutations?

• A. Ability to evade apoptosis
• B. Unlimited replication
• C. Self-sufficiency from growth signals
• D. Genetic Stability