Control of cell division/Cancer

Figure 12.1 The functions of cell division Reproduction Growth and development Tissue repair

Figure 12.5 The cell cycle

Figure 12.4 Chromosome duplication and distribution during mitosis

Figure 12.5 The cell cycle

Figure Origins of replication in eukaryotes

Figure 12.5 The cell cycle

Figure 12.6 The stages of mitotic cell division in an animal cell: G 2 phase; prophase; prometaphase

Figure 12.6 The stages of mitotic cell division in an animal cell: metaphase; anaphase; telophase and cytokinesis.

Cytokinesis in plants.

Cell Cycle control The interesting stuff! –How do cells “decide” whether and when to divide? –Checkpoints –What happens when cell cycle control is lost?

Figure 12.5 The cell cycle

Figure Mechanical analogy for the cell cycle control system Figure The G1 checkpoint

Cell and Organismal Biology 2009

Figure Evidence for cytoplasmic chemical signals in cell cycle regulation

Figure Molecular control of the cell cycle at the G 2 checkpoint MPF-Mitosis promoting factor

Figure The effect of a growth factor on cell division Fetal Calf Serum Experiment Results

Figure Density-dependent inhibition of cell division

Loss of control of the cell cycle: Cancer

Types of Cancer Epithelial cell tumors (Carcinoma) –Adenoma-benign –Adenocarcinoma-malignant glandular Connective tissue or muscle cell tumors (Sarcoma) –Chondroma-benign –Chondrosarcoma-malignant cartilage tumor Others –Leukemias and nervous system cancers

Progression of tumor size- Breast cancer doubling time is 100 days Mammogram: normal (left) and cancerous (right)

Cancers are progressive Epithelial cell tumor

Steps in the process of metastasis

Papanicolaou test “Pap smear” A. Normal cells- well differentiated B. Precancerous-abnormal differentiation C. Invasive carcinoma-undifferentiated

Cancer incidence as a function of age Colon cancer in women in England and Wales Suggests multiple mutations required to induce cancer

So how is cancer caused? Genes involved in cell cycle regulation are mutated

Genes controlling cell division that can cause cancer Oncogenes- these are mutated proto-oncogenes which push cells towards cell division (GF receptors, myc, ras etc) Tumor-suppressor genes-these are genes that stop cells from dividing (retinoblastoma, p53 APC etc)

Importance of Structure-an example P53 Mutated in 50% of all human cancers

Cell and Organismal Biology 2009

Figure Genetic changes that can turn proto-oncogenes into oncogenes

Genes controlling cell division that can cause cancer Oncogenes- these are mutated proto-oncogenes which push cells towards cell division (GF receptors, myc, ras etc) –ras-mutated in 20-30% of all cancers –GF receptors-increased in number in many breast cancers –src kinase- mutated/affected in 2-5% of cancers Tumor-suppressor genes- these are genes that stop cells from dividing –P53-mutated in 50% of cancers –Rb-mutated in 40% of cancers

Genes controlling cell division that can cause cancer Oncogenes- these are mutated proto-oncogenes which push cells towards cell division (GF receptors, myc, ras etc) –ras-mutated in 20-30% of all cancers –GF receptors-increased in number in many breast cancers –src kinase- mutated/affected in 2-5% of cancers Tumor-suppressor genes- these are genes that stop cells from dividing –P53-mutated in 50% of cancers –Rb-mutated in 40% of cancers

Science, Vol 274. Oct 18,1996. p430

Types and causes of mutations Rearrangements –Ionizing radiation- forms free radicals that damage DNA Translocation Duplications Inversions deletions –Spontaneous mutagenesis- slipped mispairing Point mutations –UV light- pyrimidine dimers –Chemical mutagenesis

Figure Nucleotide excision repair of DNA damage Xeroderma pigmentosum

Chemical mutagenesis

Ames test Aflatoxin-from the fungus aspergillus that grows on rotting peanuts

Viruses cause cancer RNA viruses (retroviruses). Cause cancer by adding oncogenes to cells. –Pick up RNA copies of proto-oncogenes and transfer them to other cells by infection DNA viruses. Cause cancer by blocking tumor-suppressor proteins.

Figure Genetic changes that can turn proto-ocogenes into oncogenes

Viruses cause cancer RNA viruses (retroviruses). Cause cancer by adding oncogenes to cells. DNA viruses. Cause cancer by blocking tumor-suppressor proteins. –Viruses produce proteins that bind to p53 and RB

DNA viruses produce proteins that block tumor- suppressor action. Normal Virus infected (SV40/papillomavirus)

Not all cancers are alike!