Cancer Biology and Loss of Cell Cycle Control (2C) - Bio & Biochem

1. What is the key role of p21 in cell cycle control?

   Cyclin-dependent kinase inhibitor that enforces $G_1$ arrest. p21 blocks cyclin-CDK activity to prevent progression from $G_1$ to S phase during stress.

2. Identify the term for cancer cell growth without attachment to a surface or matrix.

   Loss of anchorage dependence (anchorage-independent growth). Cancer cells evade anchorage requirements, allowing growth in suspension and metastasis.

3. What is a tumor suppressor gene?

   A gene that restrains proliferation; loss-of-function promotes cancer. Tumor suppressor genes inhibit cell division; their inactivation removes brakes on proliferation, facilitating cancer development.

4. Which BCL-2 family member is classically anti-apoptotic and often overexpressed in cancer?

   BCL-2. BCL-2 inhibits apoptosis by preventing mitochondrial permeabilization, promoting cancer cell survival.

5. What is anchorage dependence?

   Requirement for attachment to extracellular matrix to proliferate. Anchorage dependence ensures cells proliferate only when adhered, maintaining tissue architecture.

6. Which mutation pattern is typical for tumor suppressor genes: dominant or recessive at the cellular level?

   Recessive (both alleles usually must be inactivated). Tumor suppressor mutations are recessive as both copies must be lost to eliminate inhibitory function.

7. What is the hallmark feature of caspases in apoptosis?

   Cysteine proteases that cleave proteins after aspartate residues. Caspases dismantle cellular components specifically during apoptosis to ensure controlled demise.

8. Which term describes a tumor that invades surrounding tissue and can spread to distant sites?

   Malignant tumor. Malignant tumors exhibit invasive behavior, enabling distant spread and increased lethality.

9. What is the primary role of Rb (retinoblastoma protein) at the $G_1/S$ transition?

   Binds E2F to prevent S-phase gene transcription. Rb sequesters E2F transcription factors, inhibiting genes needed for DNA synthesis in S phase.

10. What is the main function of p53 in preventing cancer?

    Induces p21, cell cycle arrest, DNA repair, or apoptosis after damage. p53 acts as a guardian by activating responses to prevent propagation of damaged DNA in cells.

11. Which mutation pattern is typical for oncogenes: dominant or recessive at the cellular level?

    Dominant (one activating allele is sufficient). Oncogene mutations act dominantly because a single altered copy can overactivate proliferation signals.

12. What is an oncogene?

    A gain-of-function mutated gene that promotes cell division. Oncogenes drive excessive cell growth by enhancing pathways that stimulate proliferation when mutated.

13. What is a proto-oncogene?

    A normal gene that can become an oncogene after activating mutation. Proto-oncogenes regulate normal cell growth but can transform into oncogenes via mutations that increase their activity.

14. What is the extrinsic apoptosis trigger?

    Death receptor signaling (for example, Fas receptor activation). Extrinsic pathway initiates apoptosis via external signals binding death receptors on the cell surface.

15. What is the two-hit hypothesis for tumor suppressor genes?

    Both alleles must be inactivated to lose tumor suppressor function. The hypothesis explains that complete loss of tumor suppressor activity requires mutations in both gene copies.

16. What is apoptosis?

    Programmed cell death with caspase activation and minimal inflammation. Apoptosis eliminates damaged cells orderly, preventing inflammation unlike necrosis.

17. What is the immediate effect of a loss-of-function mutation in RB1 on the cell cycle?

    Constitutive E2F activity and inappropriate S-phase entry. Mutated RB1 fails to repress E2F, allowing unchecked transcription and cell cycle progression.

18. What is contact inhibition?

    Normal cells stop proliferating when they touch neighboring cells. Contact inhibition prevents overcrowding by signaling cells to stop dividing upon neighbor contact.

19. What cell cycle checkpoint is primarily regulated by p53 in response to DNA damage?

    The $G_1/S$ checkpoint. p53 halts progression at $G_1/S$ to allow DNA repair or apoptosis if damage is detected.

20. What is the defining cellular characteristic of cancer related to cell cycle control?

    Loss of normal cell cycle regulation causing uncontrolled proliferation. Cancer arises from dysregulation allowing cells to divide without normal checkpoints, leading to tumor formation.

21. What is the effect of telomerase activation in cancer cells?

    Maintains telomeres, enabling replicative immortality. Telomerase extends chromosome ends, countering shortening that limits divisions in normal cells.

22. Identify what phosphorylation of Rb by cyclin-CDK complexes causes.

    Releases E2F, enabling S-phase entry. Cyclin-CDK phosphorylation inactivates Rb, freeing E2F to transcribe S-phase promoting genes.

23. Which term describes a tumor that remains localized and does not invade nearby tissue?

    Benign tumor. Benign tumors grow locally without invading or spreading, posing less risk than malignant ones.

24. What is metastasis?

    Spread of cancer cells to distant sites via blood or lymph. Metastasis allows cancer to colonize new sites, complicating treatment and worsening prognosis.

25. What is the intrinsic (mitochondrial) apoptosis trigger?

    Internal stress such as DNA damage causing cytochrome $c$ release. Intrinsic pathway responds to cellular damage by mitochondrial release of pro-apoptotic factors.

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