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The Role of Tumor Suppressor Genes in Cancer: Knudson Hypothesis &  Oncogenes

The Role of Tumor Suppressor Genes in Cancer: Knudson Hypothesis & Oncogenes

The focus of this article is Tumor Suppressor Genes. There are various different types of tumor suppressor genes, with BRCA being one of the most popular. The role of Tumor Suppressor Genes in Cancer, Oncogenes and Knudson Hypothesis are also discussed.

Key Takeaways

  • Tumor suppressor genes help prevent tumor formation by controlling cell growth.
  • Mutations in these genes can lead to cancer by disrupting their normal functions.
  • Examples include p53, BRCA1, BRCA2, and PTEN.
  • The Knudson Two-Hit Hypothesis explains how mutations in these genes can lead to cancer.
  • Understanding tumor suppressor genes aids in developing cancer treatments.

What are Tumor Suppressor Genes?

Tumor suppressor genes are anti-oncogenes that play a role in cell division and replication. Mutations in these genes can lead to uncontrolled cell growth and cancer. There are many different tumor suppressor genes, each with its own function.

Some of the more well-known tumor suppressor genes include the p53 gene, the BRCA1 and BRCA2 genes, and the PTEN gene. The p53 gene is involved in cell cycle control and DNA repair. Mutations in this gene are found in over 50% of all human cancers. The BRCA1 and BRCA2 genes control DNA repair and cell death. These genes increase the risk of breast and ovarian cancer when they are mutated. The PTEN gene is involved in cell signaling and cell growth. Mutations in this gene are found in many different types of cancer, including breast, brain, and prostate cancer.

Normal Tumor Suppressor Gene

What is the Role of Tumor Suppressor Genes in Cancer?

Tumor suppressor genes play an important role in cancer. As the name suggests, tumor suppressor genes help to prevent tumor formation. They do this by regulating cell growth and division. When these genes are mutated, they can no longer perform their normal function, leading to uncontrolled cell growth and tumor formation. Some tumors do not contain mutated tumor suppressor genes, even though mutations in tumor suppressor genes may cause cancer. In fact, most tumors arise from other causes, such as lifestyle choices or environmental factors. However, understanding the role of tumor suppressor genes in cancer can help us to develop better treatments and improve our chances of survival.

While mutations in tumor suppressor genes can lead to cancer, not all tumors have mutated tumor suppressor genes. In fact, most tumors arise from other causes, such as lifestyle choices or environmental factors. However, understanding the role of tumor suppressor genes in cancer can help us to develop better treatments and improve our chances of survival.

Tumor Suppressor Genes and Oncogenes

There are two main types of genes that can lead to cancer: tumor suppressor genes and oncogenes. Tumor suppressor genes help to keep cells healthy and prevent them from becoming cancerous. Oncogenes, on the other hand, promote cell growth and division. Mutations in either type of gene can cause cancer.

Tumor suppressor genes are usually recessive, which means that both copies of the gene must be mutated for the gene to have any effect. Oncogenes are usually dominant, which means that only one copy of the gene needs to be mutated for the gene to have an effect.

Mutations in tumor suppressor genes are more common in cancer than mutations in oncogenes. This is because there are more copies of tumor suppressor genes in the genome than oncogenes. In addition, tumor suppressor genes are often found in regions of the genome that are prone to mutations. For example, the p53 gene is located in a region of the genome that is frequently rearranged in cancer cells.

Examples of Tumor Suppressor Genes

p53 Genes

The p53 gene is a tumor suppressor gene that is involved in cell cycle control and DNA repair. Mutations in this gene are found in over 50% of all human cancers. The p53 protein is known as the 'guardian of the genome'. It aids in the prevention of mutations by repairing DNA damage and slowing down cellular division. The p53 protein is located in the nucleus of cells, where it controls cell proliferation. When DNA damage occurs, the p53 protein is activated, stopping the cell from dividing. This gives the cell time to repair the DNA damage. If the DNA damage is too severe, the p53 protein will cause the cell to die (apoptosis).

BRCA

The BRCA1 and BRCA2 genes are tumor suppressor genes that control DNA repair and cell death. These genes increase the risk of breast and ovarian cancer when they are mutated. The BRCA proteins help to mend DNA double-strand breaks. These breaches can be induced by ionizing radiation or certain chemicals, and they may occur spontaneously. When the BRCA proteins are functioning properly, they help to prevent these DNA double-strand breaks from becoming mutations.

Location of BRCA genes

PTEN

The protein tyrosine phosphatase, non-receptor type 2 (PTEN) gene is a tumor suppressor gene that plays a role in cell signaling and growth. This gene has been linked to several different types of cancer, including breast, brain, and prostate cancer. The PTEN protein is a negative regulator of the PI3K/AKT signaling pathway. This pathway is important for cell growth, cell proliferation, and cell survival. PIP3K phosphorylates PIP3, which activates PI3K/AKT. PTEN inhibits PIP3 dephosphorylation via the activation of the PI3K/AKT signaling pathway. When PTEN is mutated or deleted, the ability of cells to regulate this pathway is lost, leading to uncontrolled cell growth.

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What is the Knudson Two-Hit Hypothesis?

The Knudson hypothesis is a theory that explains how mutations in tumor suppressor genes can lead to cancer. The hypothesis is named after Dr. Alfred G. Knudson, who first proposed the theory in 1971.

In order for a cell to become cancerous, two p53 alleles must be mutated. The first mutation can occur in any cell of the body. The second mutation must occur in a daughter cell of the first mutated cell. Once both alleles are mutated, the function of the p53 protein is lost. The loss of function of the tumor-suppressor gene, which allows the cell to become malignant, is caused by this second change.

The Knudson hypothesis can be applied to any type of cancer that arises from the loss of function of a tumor suppressor gene. For example, the hypothesis can be used to explain how mutations in the p53 gene can lead to cancer.

Schematic of Loss of Function of Tumor Suppressor Genes

The Knudson hypothesis can also be used to explain how epigenetic silencing can lead to cancer. Epigenetic silencing is the process by which a gene is turned off without changing the DNA sequence. In some cases, epigenetic silencing can lead to the loss of function of a tumor suppressor gene. For example, the p16 gene is a tumor suppressor gene that is frequently epigenetically silenced in cancer cells. The loss of function of the p16 gene leads to uncontrolled cell growth and can result in cancer.

The Knudson hypothesis is a useful theory that can help to explain how mutations in tumor suppressor genes can lead to cancer. However, the hypothesis does not explain how all types of cancer develop. For example, the hypothesis does not explain how mutations in oncogenes can lead to cancer. Despite this limitation, the Knudson hypothesis is a valuable instrument for comprehending how some types of cancer develop.


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24th Aug 2023 Niamh Murphy MSc

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