Biology of Cancer and Mutations

Learning Objectives

• Describe the main biological features of cancer cells
• Understand how mutations affect protein and cell behavior
• Details the roles of oncogenes and tumor suppressor genes in cell proliferation and death

What is Cancer?

• Cancer is a group of over 200 diseases
• Characterized by uncontrolled, abnormal cell growth
• Life-threatening if untreated
• Driven by genetic mutations

Hallmarks of Cancer

• Genome instability and mutation
• Resisting cell death
• Evading growth suppressors
• Sustained proliferative signaling

Cancer Caused by Mutations

• Mutations can change bases, increase promoter activity, and affect protein function
• Changes affect transcription factors influencing promoter activity and protein function

Cancer Genes

Proto-Oncogenes

• Normal genes involved in cell growth
• Mutations can transform them into oncogenes, driving cancer cell growth
• Examples include c-Myc and K-Ras

Oncogenes

• Mutated forms of proto-oncogenes
• Drive cancer cell growth
• Examples include activating mutations in K-Ras (found in 30-50% of colorectal cancers) and mutations of c-myc (in most Burkitt lymphoma cases)

Myc Oncogenes

• Transcription factors upregulated in response to oncogenic stimuli
• Consist of three family members (c-Myc, N-Myc, and L-Myc)
• Mutations lead to excessive Myc protein and overactivity, promoting cancer
• Amplification of the N-Myc gene is associated with poor prognosis in childhood glioblastoma

Ras GTPase

• Small GTPase proteins (N-Ras, K-Ras, H-Ras)
• Active when bound to GTP
• Crucial for activating the MAP Kinase pathway
• Mutations of Ras are common in cancers (e.g., 20-30% of colorectal cancers)

Signaling Pathways from EGFR

• Elaborate signaling pathway starting with EGF
• Involves multiple proteins (Shc, Ras, SOS, Grb2, PI3K, PIP2, PLCγ, DAG, IP3, PKC, Raf, MEK, ERK, NF-κB, Akt, Calcineurin, NEKB)
• Leads to downstream effects, including gene expression

Tumor Suppressor Genes

• Inhibit cell growth and function
• Mutations can contribute to uncontrolled cell division and cancer
• Examples include RB1 and TP53

DNA Repair/Stability Genes

• Maintain DNA stability and repair mutations
• Mutations in these genes can lead to accumulating mutations and increase cancer risk
• Examples include BRCA1 and BRCA2

TP53 and P53

• TP53 gene encodes the transcription factor P53 (tumor protein 53)
• One of the most commonly mutated genes in cancers
• Acts as a tumor suppressor, regulating genes involved in proliferation and apoptosis preventing cancer formation
• Often mutated or not functional in cancers where it can't regulate proliferation or apoptosis

Programmed Cell Death (Apoptosis)

• A natural cell death process
• Extrinsic pathway—external signals trigger apoptosis
• Intrinsic pathway—internal stress signals trigger apoptosis
• Critical for maintaining cellular homeostasis and eliminating damaged or unwanted cells.

RB1 (Retinoblastoma)

• Inhibits E2F transcription factors and cell cycle progression
• Phosphorylation inactivates RB1

BCL-2 Proteins

• Regulate apoptosis
• Some (e.g., BCL-2) inhibit apoptosis, others (e.g., Bax) promote it.
• Mutations could lead to altered apoptosis regulation and impact cancer development

This quiz explores the biological features of cancer cells, the impact of mutations on protein and cell behavior, and the roles of oncogenes and tumor suppressor genes. Understand the hallmarks of cancer and how genetic changes contribute to the disease. Test your knowledge on cancer genetics and cell proliferation.