6. Tumour Suppressor Genes (Retinoblastoma and the two hit hypothesis, p53)

Summary

This video explains the role of tumor suppressor genes in cancer development. Tumor suppressor genes, like the retinoblastoma (RB) and p53 genes, regulate cell growth and division. Mutations in these genes, such as the loss of function in RB and p53, lead to uncontrolled cell division and cancer. The video covers the two-hit hypothesis, where both gene copies must mutate for cancer to develop. It also explains the difference between inherited and spontaneous mutations, with inherited mutations leading to earlier and more frequent tumor development. The video emphasizes the importance of tumor suppressor genes in regulating the cell cycle and preventing cancer formation.

Takeaways

• 😀 Tumor suppressor genes inhibit cell growth and division, preventing the formation of tumors.
• 😀 Proto-oncogenes promote cell growth, but when mutated, they become oncogenes and contribute to cancer.
• 😀 Loss-of-function mutations in tumor suppressor genes can lead to cancer development.
• 😀 Tumor suppressor genes are recessive, requiring both copies to be mutated for cancer to develop.
• 😀 Retinoblastoma (RB) is a key tumor suppressor gene involved in controlling the G1 checkpoint in the cell cycle.
• 😀 The RB protein prevents DNA replication by inhibiting the E2F transcription factor, halting cell division.
• 😀 The two-hit hypothesis explains that both copies of a tumor suppressor gene must be mutated for cancer to occur.
• 😀 Inherited mutations in the RB gene lead to earlier onset of retinoblastomas and more frequent tumor occurrences.
• 😀 Spontaneous mutations in the RB gene require two mutations to occur, leading to cancer later in life.
• 😀 p-53 is the 'king of tumor suppressors,' playing a crucial role in responding to DNA damage by halting the cell cycle or inducing apoptosis.
• 😀 Mutations in p-53 are found in approximately 50% of cancers and can lead to uncontrolled cell division and cancer progression.

Q & A

What are tumor suppressor genes and how do they function in cancer development?

Tumor suppressor genes are genes that code for proteins that inhibit cell growth and division. These genes prevent the formation of tumors by acting as brakes on the cell cycle. When these genes are mutated, they can no longer perform their function, leading to uncontrolled cell growth and potentially cancer development.

How are tumor suppressor genes different from proto-oncogenes?

Tumor suppressor genes inhibit cell growth and division, acting as brakes on the cell cycle. Proto-oncogenes, on the other hand, promote cell growth and division. When mutated, proto-oncogenes become oncogenes, which can drive cancer development by promoting excessive cell division.

What is the two-hit hypothesis in the context of tumor suppressor genes?

The two-hit hypothesis states that both copies of a tumor suppressor gene need to be mutated for cancer to develop. The first mutation (the 'first hit') may be inherited or spontaneous, and the second mutation (the 'second hit') in the same gene in a single cell leads to the loss of its tumor-suppressing function.

Can you explain the role of the retinoblastoma (RB) gene in cancer development?

The retinoblastoma (RB) gene codes for a protein that controls the G1 checkpoint in the cell cycle. RB inactivates the E2F transcription factor, preventing the cell from moving into S phase. If the RB gene is mutated and produces a nonfunctional protein, the cell can bypass the checkpoint and continue dividing uncontrollably, leading to tumor development.

What happens when the retinoblastoma gene is mutated?

When the retinoblastoma (RB) gene is mutated, the RB protein cannot bind to and inactivate the E2F transcription factor, allowing the cell to proceed into S phase and begin DNA replication uncontrollably. This loss of control can contribute to cancer development.

How does the inheritance of the RB gene mutation affect the risk of developing retinoblastoma?

In inherited cases of retinoblastoma, one mutated copy of the RB gene is inherited from a parent. This means that every cell in the body has one faulty copy from birth. A second mutation (the 'second hit') is required in any cell for cancer to develop, leading to the formation of tumors, often at a younger age.

How do spontaneous mutations in the RB gene differ from inherited mutations in terms of cancer development?

In spontaneous mutations, both copies of the RB gene must be mutated in a single cell to cause cancer. Since both mutations need to occur spontaneously, this process generally takes longer and usually results in the development of tumors later in life, as compared to inherited mutations which lead to earlier onset of cancer.

Why is the p53 gene referred to as the 'king of tumor suppressors'?

The p53 gene is considered the 'king of tumor suppressors' because it plays a crucial role in preventing cancer development by activating cell cycle arrest and apoptosis in response to DNA damage or stress. When p53 is mutated, cells can continue to divide uncontrollably, contributing to tumor formation.

What happens when p53 is mutated in cancer cells?

When the p53 gene is mutated, the protein it produces cannot effectively stop the cell cycle or initiate apoptosis in response to DNA damage. This allows damaged cells to divide without control, accumulating mutations and increasing the risk of cancer development.

What is Li-Fraumeni syndrome, and how is it related to mutations in the p53 gene?

Li-Fraumeni syndrome is a rare genetic disorder caused by inherited mutations in the p53 gene. People with this syndrome have a much higher risk of developing cancer, with approximately 50% of individuals developing cancer by the age of 30 due to the loss of p53's tumor-suppressing functions.