Oncogenes and Tumor Suppressors - Online Tutor, Practice Problems & Exam Prep

Cancer cells exhibit unique properties such as uncontrolled growth, insensitivity to anti-growth signals, evasion of apoptosis, and genetic instability. These characteristics arise from mutations in oncogenes and tumor suppressor genes. Oncogenes, like RAS, promote cell proliferation when overexpressed, while tumor suppressors, such as p53, prevent tumor formation by regulating cell cycle and DNA repair. Loss of tumor suppressor function leads to increased mutations and tumor development, highlighting the critical balance between these gene types in cancer progression.

Oncogenes and Tumor Suppressors

Hi. In this video, I'm going to be talking about oncogenes and tumor suppressors. So, first, I just want to talk about cancer as a whole. Cancer cells have a variety of different properties. Now I just want to go over a few of these properties before moving on to talking about the specific mutations in specific genes that give them these properties. Cancer cells have a variety of mutations and these give them certain properties. The first is sort of growth without growth signals. These 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 anti-growth 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 apoptosis or cell death. Right? So these cells obviously aren't dying even though they're being told to, so they're just like, "I'm ignoring that and I'm just gonna grow." Then they also have unlimited replication. So generally, cells, you know, can't just replicate all the time. It's why we have cell death. But cancer cells, obviously, they form these large tumors, travel 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 in the tumor, 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 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, there's a lot of them and they usually provide the cancer cells with at least one of these seven properties if not multiple at the same time.

So let's talk about the first type of genes. These are called oncogenes, and these are mutated genes that become overexpressed and support cancer growth. Oncogenes, when mutated, become really highly expressed, and the expression of those genes leads to one or more of those seven things we previously talked about. So, oncogenes can become oncogenes through mutations or through gene amplification. So, obviously, we're talking about being overexpressed. So if a gene that is an oncogene is not necessarily directly mutated, but copied multiple times and duplicated, then you have twice the amount of gene, and you get twice the amount of expression, and that's overexpression as well. We call proto-oncogenes sort of the normal, not mutated versions, but they obviously become oncogenes when mutated. So because the oncogenes are being overexpressed, generally, what they cause is cell proliferation, survival, and tumor development. And so, typical oncogenes are things like growth factors, which when mutated, overexpressed, and stimulate a lot of growth. They're receptors that stimulate growth signaling pathways. GTP-binding proteins, which we have seen have a ton of responsibilities in the cell for signaling, including protein kinases, receptor or non-receptor transcription factors. You can imagine if transcription factors are overexpressed, then you're going to be transcribing a bunch of the cell. So all of these pathways, you can imagine how if any of these things are overexpressed, 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 RAS. We've talked about RAS before mainly in terms of signaling. So remember, RAS is a GTPase, but it's also an oncogene. And so when it's mutated, we call it an oncogene, and it's actually mutated in 20% of human cancers. So 20% of all the human cancers that exist in the world are due to the fact that RAS has some kind of mutation. So that's like insane, right? Because if RAS is overexpressed, then you have all these other pathways being overexpressed. 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 mutation in DNA. We'll say this is RAS. This becomes activated through some more additional mutations and can lead to the cancer cell development. So remember, oncogenes are going to be overexpressed and have a high level or increased levels of activity. Then the exact opposite of that is going to be tumor suppressors, and these are genes that when mutated result in a loss of activity and lead to cancer. So the activity loss of tumor suppressors, so tumor suppressors are mutated, so they're lost to the cells, that function that they have is lost, and that leads to cell proliferation, survival, and tumor development. So an example of this is p53. We've talked about p53 before in signaling, and it's a transcription factor, and it is also a tumor suppressor. So normally, p53 in the cell responds to DNA damage and tells the cell, "Hey, you have DNA damage, you need to repair." Well, the cancer cells don't want that. Right? They want this accumulation of mutations, this accumulation of damage. So what they do is they mutate p53, so it can't work. So, when the activity of p53 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 and it affects p53. When p53 is not here, then that's going to block the apoptosis pathway and death of cells. It's also going to block cell cycle checkpoint, DNA repair, and cell cycle restart. So none of this is going to happen. So you can imagine that even if there's DNA damage, the cell is just going to go and divide, and it's going to have no idea. So it can't repair that, which is obviously bad for us, but great for a pure tumor cell.

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

Here’s what students ask on this topic:

What are oncogenes and how do they contribute to cancer development?

Oncogenes are mutated genes that become overexpressed and support cancer development. They originate from normal genes called proto-oncogenes, which regulate cell growth and division. When proto-oncogenes mutate, they become oncogenes, leading to uncontrolled cell proliferation. This overexpression can occur through mutations or gene amplification. Oncogenes contribute to cancer by promoting cell survival, proliferation, and tumor development. For example, the RAS gene, when mutated, is involved in 20% of human cancers. It leads to the activation of multiple signaling pathways that drive cancerous growth. Thus, oncogenes play a crucial role in the transformation of normal cells into cancerous ones.

What is the role of tumor suppressor genes in preventing cancer?

Tumor suppressor genes are crucial in preventing cancer by regulating cell cycle progression, promoting DNA repair, and inducing apoptosis in damaged cells. When these genes are functional, they act as a safeguard against uncontrolled cell growth. A well-known example is the p53 gene, which responds to DNA damage by halting the cell cycle and initiating repair mechanisms. If the damage is irreparable, p53 can trigger apoptosis to prevent the propagation of mutated cells. However, when tumor suppressor genes like p53 are mutated and lose their function, cells can proliferate uncontrollably, leading to tumor development. Thus, the loss of tumor suppressor activity is a significant factor in cancer progression.

How do cancer cells evade apoptosis?

Cancer cells evade apoptosis through several mechanisms, often involving mutations in genes that regulate cell death. One common way is by mutating tumor suppressor genes like p53, which normally induce apoptosis in response to DNA damage. Without functional p53, cells with damaged DNA can continue to divide. Additionally, cancer cells may overexpress anti-apoptotic proteins or downregulate pro-apoptotic proteins, tipping the balance in favor of survival. These alterations allow cancer cells to ignore signals that would typically trigger cell death, contributing to their unchecked growth and the formation of tumors.

What is the significance of the RAS gene in cancer?

The RAS gene is highly significant in cancer because it is involved in about 20% of all human cancers. RAS is a GTPase that plays a critical role in cell signaling pathways that control growth and differentiation. When mutated, RAS becomes constitutively active, continuously sending growth signals to the cell even in the absence of external stimuli. This leads to uncontrolled cell proliferation and contributes to tumor development. The persistent activation of RAS can also activate other downstream signaling pathways, further promoting cancerous behaviors. Therefore, mutations in the RAS gene are a major driver of cancer progression.

How do mutations in tumor suppressor genes lead to cancer?

Mutations in tumor suppressor genes lead to cancer by eliminating the cell's ability to regulate growth and repair DNA damage. Tumor suppressor genes, such as p53 and retinoblastoma (RB), normally function to control cell cycle checkpoints, repair DNA, and induce apoptosis in damaged cells. When these genes are mutated, their protective functions are lost. For instance, a mutated p53 gene cannot halt the cell cycle or initiate DNA repair, allowing cells with genetic damage to continue dividing. This accumulation of mutations and unchecked cell proliferation ultimately leads to tumor development. Thus, the loss of tumor suppressor gene function is a critical step in cancer progression.