Question

The \(r b\) gene encodes a protein that inhibits \(\mathrm{E} 2 \mathrm{~F}\), a transcription factor that activates several genes involved in cell division. Mutations in \(r b\) are associated with certain forms of cancer, such as retinoblastoma. Under each of the following conditions, would you expect the cancer to occur? A. One copy of \(r b\) is defective; both copies of \(E 2 F\) are functional. B. Both copies of \(r b\) are defective; both copies of \(E 2 F\) are functional. C. Both copies of \(r b\) are defective; one copy of \(E 2 F\) is defective. D. Both copies of \(r b\) and \(E 2 F\) are defective.

Short answer

Cancer might occur in scenarios B and C, where there are multiple defective \(r b\) genes, potentially leading to unregulated \(\mathrm{E} 2 \mathrm{F}\). However, in scenarios A and D, it is unlikely that cancer will occur as either both \(r b\) are not defective or an \(E 2 F\) is defective.

Step-by-step solution

Analyze Scenario A

This scenario describes a situation where one copy of \(r b\) is defective and both copies of \(\mathrm{E} 2 \mathrm{F}\) are functional. Given that not all \(r b\) is defective, there would still be some regulation of \(\mathrm{E} 2 \mathrm{F}\) activity. Therefore, this may not necessarily lead to cancer.

Analyze Scenario B

Here, both copies of \(r b\) are defective, with both copies of \(\mathrm{E} 2 \mathrm{F}\) functional. This is likely to lead to unregulated \(\mathrm{E} 2 \mathrm{F}\) activity and potentially uncontrolled cell division, thereby increasing the risk of cancer.

Analyze Scenario C

In this case, both copies of \(r b\) and one copy of \(\mathrm{E} 2 \mathrm{F}\) are defective. It is probable that the functional copy of \(\mathrm{E} 2 \mathrm{F}\) could be unregulated and lead to cancer.

Analyze Scenario D

In this last scenario, both copies of \(r b\) and \(\mathrm{E} 2 \mathrm{F}\) are defective. Since \(\mathrm{E} 2 \mathrm{F}\) plays a key role in cell division, if it's defective, it may not be able to activate cell division, even in the absence of \(r b\). As such, this scenario may not necessarily lead to cancer.

Key concepts

Rb gene

The Rb gene plays a crucial role in regulating the process of cell division. It encodes a protein known as the retinoblastoma protein (Rb), which acts as a tumor suppressor. Essentially, the Rb protein helps to keep cell growth and division in check by inhibiting the activity of E2F transcription factors. When the Rb protein is functional, it binds to E2F, preventing it from activating genes necessary for cell cycle progression from G1 to S phase, where DNA replication occurs.

If there is a mutation in the Rb gene, the production of functional Rb protein can be affected. This loss of function can lead to uncontrolled cell division as E2F is no longer inhibited. This process is particularly significant in the development of certain cancers, like retinoblastoma, where mutations in both copies of the Rb gene can lead to the loss of its critical regulatory function.

In summary, the Rb gene is vital in preventing unregulated cell proliferation, and its malfunction is closely linked to cancer development.

E2F transcription factor

E2F transcription factors are essential in regulating the genes that are needed for cell cycle progression and DNA replication. When E2F transcription factors are active, they bind to the DNA and promote the expression of genes that facilitate the transition from the G1 phase to the S phase in the cell cycle.

The activity of E2F is tightly regulated by the Rb protein. In normal conditions, Rb binds to E2F, preventing it from activating cell cycle genes. When a cell is signaled to divide, Rb is phosphorylated, causing E2F to be released. Once free, E2F can activate the necessary genes for cell division. However, if Rb is mutated and cannot bind E2F, the E2F transcription factor may be constantly active, leading to excessive cell division, which is a hallmark of cancerous growths.

This precise control of E2F activity is pivotal to maintaining order within the cell cycle and ensuring that cells only divide when it is appropriate.

Cell division

Cell division is an essential process for growth, development, and repair in organisms. It occurs in a highly regulated manner to ensure that cells divide at the right place and time. The cell cycle is the mechanism through which cell division is controlled. It includes phases such as G1 (cell growth), S (synthesis of DNA), G2 (preparation for mitosis), and M (mitosis).

The transition between these phases is controlled by various proteins, including the Rb protein and E2F transcription factors. Proper regulation is necessary to avoid uncontrolled cell division that can lead to tumors and cancer.

If regulatory proteins like Rb or E2F are mutated, it can result in the loss of control over cell division, promoting cell proliferation beyond the normal limits. This can lead to an accumulation of cells, forming a tumor. Thus, understanding cell division regulation provides insights into cancer growth and development.

Cancer genetics

Cancer genetics is the study of genetic mutations and alterations that contribute to cancer development. At its core, cancer is a genetic disease caused by changes in DNA that affect cell growth and division. These changes can be inherited or acquired during a person's lifetime.

Genetic mutations in tumor suppressor genes like Rb or oncogenes like E2F transcription factors can lead to loss of control over cell cycle regulation, resulting in unregulated cellular division. Tumor suppressor genes generally encode proteins that restrain cell division, repair DNA mistakes, or tell cells when to die (apoptosis). When these genes are mutated, their regulatory function is lost, leading to increased cancer risk.

In contrast, oncogenes typically promote cell division and survival. When these genes become overactive due to mutations, they can drive cells to divide uncontrollably.

Research into cancer genetics is pivotal in developing targeted therapies that can address the specific genetic alterations present in individual cancers, leading to more effective and personalized cancer treatment strategies.