Chapter 16 – Cell Cycle Regulation and Cancer
Cancer is a Genetic Disease
• Single nucleotide substitutions to large scale rearrangements of the genome are associated with
• Unlike other diseases, cancer is attributed to mutations that arise predominantly in somatic
– Rarely the result of a single mutation, rather an accumulation of mutations (sometimes
Cancer is abnormal cell growth (benign tumor)
Abnormal restraints that keep cells from spreading and invading other parts of the body
o Billions of cells
o Originated from one common ancestral cell
Important for its causes, diagnosis and prognosis.
o Reciprocal translocations between chromosome 8 (breakpoint near c-myc gene) and
chromosomes 2,14 or 22 near the immunoglobulin genes.
In every patient, all the lymphoma cells have the same breakpoints.
Each patient will have their own unique breakpoint.
The genetic basis for cancer is usually the
accumulation of several mutations.
Defects in Genome Stability and DNA Repair
• Cancer cells show higher rates of mutation,
chromosomal abnormalities and genomic
– Mutator phenotype
• Chronic Myelogenous Leukemia (CML)
– Philadelphia chromosome
– C-ABL gene fused to BCR gene
• BCR-ABL fusion product is an abnormal signal transduction molecule stimulating
cell proliferation in absence of growth signals. DNA Repair Defects
• Xeroderma pigmentosum
– Defective in nucleotide excision repair
– Sensitive to UV light
– Often develop skin cancer
• Hereditary Nonpolyposis Colorectal Cancer (HNPCC)
– Defect in DNA mismatch repair
– Increased risk of developing colon, ovary, uterine and kidney cancers
Cell Cycle Regulation
• In addition to regulation at the checkpoints, cells control progression through cycle with:
– Cyclins and CDKs (cyclin-dependent kinases)
• The cell synthesizes and destroys cyclins in a precise pattern during cell cycle.
• Cyclins bind to their specific CDK which activates the CDK/cyclin complex
– Selectively phosphorylates and activates other proteins to bring about
advance in cell cycle.
• If DNA damage can’t be repaired, then the cell will activate programmed cell death (apoptosis).
• Genetically controlled event leading to cell suicide
– Nuclear DNA becomes fragmented
– Internal cellular structures disrupted
– Cell dissolves into small spherical bodies.
• Carried out by caspases (proteases) M