MODULE 45

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Questions and Answers

What role does p53 play in the apoptotic process?

p53 blocks the effects of anti-apoptotic proteins.

p53 is a cell surface receptor for death signals.

p53 directly initiates cell division.

p53 induces an apoptotic effector cascade. (correct)

Which of the following proteins is classified as pro-apoptotic?

BCL-XL

BAX (correct)

BCL-2

TNF-R1

What is the primary consequence of the release of cytochrome C from mitochondria?

It initiates DNA replication.

It activates intracellular proteinases.

It triggers the activation of caspases. (correct)

It blocks pro-apoptotic signaling.

Which factor is commonly mutated in more than 50% of human cancers?

p53 Signup and view all the answers

Which of these statements accurately describes the properties of cancer cells?

Cancer cells evade the mechanisms of apoptosis. Signup and view all the answers

What is the primary difference in signaling between normal cells and cancer cells with respect to growth stimulation?

Cancer cells exhibit a predominant use of autocrine signaling. Signup and view all the answers

Which mechanism is responsible for the insensitivity of cancer cells to antigrowth signals?

Mutations in the pRB protein. Signup and view all the answers

How do RAS proteins contribute to growth signal autonomy in cancer cells?

They become active independently of upstream stimulation. Signup and view all the answers

What role do normal cells, referred to as 'bystanders,' play in the growth of cancer cells?

They supply growth and transformation signals to cancer cells. Signup and view all the answers

What mechanism prevents pRB from being active and thus blocks progression from G1 to S phase?

pRB must be hypophosphorylated. Signup and view all the answers

What common alteration in cancer cells results in evasion of apoptosis?

Loss of function of apoptosis sensors and effectors. Signup and view all the answers

Which of the following best describes alterations in extracellular matrix receptors in cancer cells?

They dictate the commitment to quiescence, apoptosis, or proliferation. Signup and view all the answers

What outcome is associated with the overexpression of oncogenes in cancer cells?

Increased resistance to apoptosis. Signup and view all the answers

Which of the following is NOT one of the six basic properties of cancer cells?

Ability to regenerate tissues Signup and view all the answers

What is the significance of driver gene mutations in cancer?

They are crucial for the initiation and progression of cancer. Signup and view all the answers

Which mutation is typically associated with the 'two-hit hypothesis' in cancer?

Tumor suppressor gene mutations Signup and view all the answers

What characteristic does the term 'limitless replicative potential' refer to in cancer cells?

Cancer cells can replicate indefinitely without entering senescence. Signup and view all the answers

Which of the following best describes the role of oncogenes?

They are mutated versions of proto-oncogenes that promote cell growth. Signup and view all the answers

Which type of mutation typically requires only one allele to be mutated to contribute to cancer?

Oncogene mutations Signup and view all the answers

What is often a consequence of sustained angiogenesis in cancer cells?

Enhanced nutrient supply to tumors Signup and view all the answers

Which hypothesis explains that multiple mutations in different genes are typically required for cancer development?

Multi-hit hypothesis Signup and view all the answers

What is a primary characteristic of growth signal autonomy in cancer cells?

Predominantly using autocrine signaling Signup and view all the answers

How do alterations in pRB function contribute to cancer cell behavior?

By allowing progression from G1 to S phase Signup and view all the answers

What role do normal bystander cells play in cancer progression?

They provide growth and transformation signals to cancer cells. Signup and view all the answers

Which of the following is a mechanism through which cancer cells evade apoptosis?

Inactivation of apoptosis sensors Signup and view all the answers

Which property allows cancer cells to grow continuously without being restricted by normal cellular mechanisms?

Counteracts growth-inhibiting factors Signup and view all the answers

What is one consequence of structural alterations in RAS proteins in human tumors?

Altered activity independent of upstream regulators Signup and view all the answers

What type of mutation is necessary for the development of cancer when it leads to the loss of function of tumor suppressor genes?

Mutation of both alleles Signup and view all the answers

Which hallmark of cancer is directly related to the capability of cancer cells to spread to distant sites?

Tissue invasion and metastasis Signup and view all the answers

What is a primary feature of altered integrin receptors in cancer cells?

Altered decisions between quiescence and proliferation Signup and view all the answers

How does modulated phosphorylation of pRB influence cancer cell proliferation?

Only hypophosphorylated pRB can bind E2F and facilitate the cell cycle. Signup and view all the answers

Which form of growth signaling in cancer cells is often fueled by mutated proto-oncogenes?

Signal transduction pathways Signup and view all the answers

What is a consequence of high apoptosis in tumors?

Tumor development requires resistance to apoptosis. Signup and view all the answers

What does the term 'sustained angiogenesis' refer to in the context of cancer cells?

Formation of new blood vessels to supply the tumor Signup and view all the answers

Which of the following alterations is a key contributor to cancer cells' insensitivity to antigrowth signals?

Mutations in pRB or its regulatory factors Signup and view all the answers

Which type of mutations does not contribute directly to the development of cancer despite being associated with it?

Passenger mutations Signup and view all the answers

What best describes the relationship between cancer cells and the extracellular environment in terms of growth signals?

Cancer cells exhibit reduced dependence on external growth stimuli. Signup and view all the answers

In which manner do cancer cells typically differ from normal cells regarding growth signals?

They resist external anti-growth signals Signup and view all the answers

Which statement accurately describes the relationship between oncogenes and proto-oncogenes?

Oncogenes are mutated, activated versions of proto-oncogenes. Signup and view all the answers

How does the 'multiple-hit hypothesis' relate to the development of colorectal cancer?

It indicates that multiple mutations in various genes are required. Signup and view all the answers

What primary characteristic defines the self-sufficiency of cancer cells in growth signals?

Ability to produce their own growth signals Signup and view all the answers

What function do sensors serve in apoptosis?

They monitor extracellular and intracellular cues regarding cell survival. Signup and view all the answers

Which protein family's members play a role in modulating the release of cytochrome C?

BCL-2 family Signup and view all the answers

What condition does p53 primarily respond to?

Hypoxia and DNA damage Signup and view all the answers

What action does BAX perform in the apoptotic process?

It stimulates the release of cytochrome C from mitochondria. Signup and view all the answers

Which of the following features is characteristic of cancer cells?

Insensitivity to anti-growth signaling Signup and view all the answers

How does p53 affect apoptotic signaling?

It upregulates pro-apoptotic factors like BAX. Signup and view all the answers

Which factor is known to regulate the effectors of apoptosis?

Intracellular proteinases Signup and view all the answers

What is the role of cytochrome C in apoptosis?

To activate caspases in the cytosol. Signup and view all the answers

Which of the following describes the relationship between p53 and cancer cells?

p53 detects oncogene overexpression. Signup and view all the answers

What key alteration do cancer cells exhibit that allows them to evade apoptosis?

Mutations in pro-apoptotic factors. Signup and view all the answers

Study Notes

Cancer versus a Corporation

Cancer cells fuel their own growth
They resist growth-inhibiting factors
They withstand adverse internal and external conditions
They grow without limit
They create their own infrastructure
They acquire resources

Six Basic Properties of Cancer

Self-sufficiency in growth signals
Insensitivity to anti-growth signals
Sustained angiogenesis
Evasion of apoptosis
Tissue invasion and metastasis
Limitless replicative potential

Role of Mutations

Driver gene mutations are crucial for cancer initiation, progression, and viability
Passenger mutations don't contribute to cancer development
Oncogenes are mutated, activated proto-oncogenes that control cell growth
Tumor suppressor genes control cell growth; mutated and lost, cancer results
Oncogenic activation usually requires mutation of one allele
Tumor suppressor mutations typically require mutation of both alleles ("two-hit hypothesis")
Most cancers require multiple mutations in different genes ("multiple-hit hypothesis")

Cancer Cell Metabolism

Otto Warburg recognized altered cancer cell metabolism in the 1920s.
Most cancers are glycolytic (high glucose usage)
Additional metabolic pathways contribute to uncontrolled proliferation

Strategies for Growth Signal (GS) Autonomy

Cancer cells predominately use autocrine signaling
Alterations in extracellular growth signals
Changes in growth signal receptors
Changes in extracellular matrix (ECM) receptors (integrins)
Modifications in intracellular signaling cascades

Insensitivity to Antigrowth Signals

Antigrowth signals often funnel through pRB proteins (p107 and p130)
E2F is a transcription factor dependent on pRB
pRB-E2F blocks progress from G1 to S phase
Resistance mechanisms include mutations in pRB or downstream factors, sequestration of pRB, or modulated phosphorylation of pRB

Rate of Proliferation vs. Attrition

Tumor growth depends on the rate of proliferation exceeding the rate of cell death (apoptosis)
Sensors monitor extracellular and intracellular cues to determine whether a cell should live or die
Cell surface receptors (e.g., FAS receptor, TNF-R1) respond to survival or death signals
Intracellular sensors respond to abnormalities such as DNA damage, high proliferation signals, or hypoxia

Apoptotic Pathways

Most apoptotic signals converge on mitochondria
Release of cytochrome C is catalyzed by BCL-2 family members (BAX, BAK pro-apoptotic; BCL-2, BCL-XL anti-apoptotic)
Cytochrome C triggers caspase activation, leading to apoptosis

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Description

This quiz explores the fundamental properties of cancer, including how cancer cells grow, evade controls, and the roles of mutations in cancer development. It also covers the distinction between driver and passenger mutations in oncogenes and tumor suppressor genes. Test your understanding of these critical concepts in cancer biology.