Rucete ✏ Campbell Biology In a Nutshell
Unit 3 GENETICS — Concept 18.5 Cancer Results from Genetic Changes That Affect Cell Cycle Control
Cancer arises when cells lose control over growth and division due to genetic mutations. Normal cellular controls that regulate growth become disrupted, often involving genes known as proto-oncogenes and tumor-suppressor genes.
Genes Associated with Cancer
Normal cell growth and division are regulated by:
Proto-oncogenes: promote normal cell division.
Tumor-suppressor genes: inhibit cell division.
Genetic mutations can convert proto-oncogenes into cancer-causing oncogenes by increasing their expression or activity.
Mutations affecting tumor-suppressor genes reduce their normal inhibitory activity, also promoting uncontrolled growth.
How Proto-Oncogenes Become Oncogenes
Four main mechanisms transform proto-oncogenes into oncogenes:
Epigenetic Changes:
Alterations in chromatin structure cause inappropriate gene activation.
Translocations:
Chromosomes break and rejoin incorrectly, placing proto-oncogenes near active promoters, boosting their expression.
Gene Amplification:
Increased copies of a proto-oncogene lead to overproduction of growth-stimulating proteins.
Point Mutations:
Mutations in regulatory regions (promoter/enhancer) enhance gene expression.
Mutations in coding regions result in proteins that are hyperactive or resistant to degradation.
Tumor-Suppressor Genes and Their Functions
Tumor-suppressor proteins normally help prevent uncontrolled growth:
Repair damaged DNA.
Maintain cell adhesion to other cells and the extracellular matrix.
Inhibit cell cycle progression.
Loss of tumor-suppressor activity removes these protective mechanisms.
Key Examples: Ras and p53 Genes
Ras proto-oncogene:
Encodes a protein involved in cell signaling pathways, promoting cell growth.
Mutations create hyperactive Ras, stimulating excessive cell division even without growth signals.
Ras mutations appear in ~30% of human cancers.
p53 tumor-suppressor gene ("guardian angel of the genome"):
Activates DNA repair genes, cell-cycle inhibitors, and apoptosis if DNA damage is irreparable.
Mutations disabling p53 lead to unchecked cell division and tumor development.
p53 mutations occur in over 50% of human cancers.
The Multistep Model of Cancer Development
Cancer usually results from an accumulation of multiple genetic mutations.
Example: Colorectal cancer progresses from benign polyps to malignant tumors through mutations in tumor-suppressor genes (APC, SMAD4, p53) and oncogenes (ras).
Cancer risk increases with age due to the gradual accumulation of these mutations.
Inherited Cancer Risk
Some cancers, like colorectal and breast cancers, involve inherited genetic mutations, increasing susceptibility:
Mutations in BRCA1 and BRCA2 genes significantly raise breast cancer risk.
Inherited colon cancer syndromes (HNPCC, APC gene mutations) greatly increase colon cancer risk.
Viruses and Cancer
Certain viruses can contribute to cancer by introducing oncogenes or disrupting tumor-suppressor genes:
Human papillomavirus (HPV) linked to cervical cancer.
Epstein-Barr virus, HTLV-1, and others also associated with specific cancers.
Modern Approaches and Treatment
Advanced genomic analysis has improved cancer classification and personalized treatments:
Breast cancer classification based on receptor profiles (e.g., ER, PR, HER2).
Treatments tailored to specific genetic mutations (e.g., Herceptin for HER2-positive breast cancer).
In a Nutshell
Cancer results from genetic alterations disrupting normal controls over cell division. Proto-oncogenes and tumor-suppressor genes are commonly mutated, leading to uncontrolled growth. Cancer develops progressively through accumulated genetic mutations, influenced by heredity, environmental factors, and viruses. Modern genomics-based approaches offer more targeted, personalized cancer treatments.