Cancer Biology and Loss of Cell Cycle Control (2C) - MCAT Biological and Biochemical Foundations of Living Systems

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

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

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.

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.

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

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

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.

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

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.

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.

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

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

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

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

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

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

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

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

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

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

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

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

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

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