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The Cell Cycle: CELLULAR REPRODUCTION. What must happen before a cell can divide (reproduce)?. Bacterial cell division (binary fission). What is different about a eukaryotic cell? What complicates eukaryotic cell division?. Figure 12.2 Eukaryotic chomosomes.
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The Cell Cycle: CELLULAR REPRODUCTION What must happen before a cell can divide (reproduce)?
What is different about a eukaryotic cell? What complicates eukaryotic cell division?
Figure 12.3 Chromosome duplication and distribution during mitosis
The functions of Mitotic cell division: 1.) Reproduction Asexual reproduction of a unicellular, eukaryotic organism
Figure 12.5 The stages of mitotic cell division in an animal cell: G2 phase; prophase; prometaphase
Figure 12.5 The stages of mitotic cell division in an animal cell: metaphase; anaphase; telophase and cytokinesis.
Testing a hypothesis for chromosome migration during anaphase
Figure 12.8 Cytokinesis in animal and plant cells http://www.youtube.com/watch?v=KE2VI7tDL1k&feature=fvwrel
Regulation of the Cell Cycle Evidence for cytoplasmic chemical signals in cell cycle regulation
Cell Regulation- -Both internal and external signals • Is the environment ok? • Did all the DNA replicate? • Are chromosomes intact? • Many factors regulate and trigger the cell to cycle. • Some cells stop dividing (neurons) some constantly divide- skin cells constantly divide
Regulatory proteins • Protein kinases- phosphorylate targets to activate or inactive- affect cell cycle progression • Cyclins- amount changes cyclically, needed to activate kinases (cdks)
Molecular control of the cell cycle at the G2 checkpoint MPF- controls G2 check point. Cyclin/cdk- phosphoylates proteins and initiates chromosome condensation, nuclear envelope disintegration. Destroys cyclin to stop itself. Increases other cyclins.
SIGNALING OF CELL CYCLE CONTROL ELEMENTS Internal signaling: M phase checkpoint- (correct spindle fiber attachment) kinetochore proteins-spindle+ spindle APC inactive active Cyclins breakdown kinetochore proteins breakdown holding sister chromatids together
External Signaling: G1 checkpoint, Growth factors Ex. PDGF receptor cell cycle control
-Density-dependent inhibition -Anchorage dependence Fibroblast growth
Breast cancer BIOLOGY OF CANCER Cancer is the loss of normal cell cycle regulation (a cell starts dividing out of control) 200 different kinds US: 10 million new cases/year1/3 people in their life time will develop some form of cancer Characteristics of Cancer Cells: Different appearance, De-differentiation (like stem cells) Loss of cell cycle control & contact inhibition, Heritable- daughter cells also cancerous Transplantablitity, Increased mutation rate Ability to spread (metastasis) & induce local blood vessel formation (angiogenesis)
BIOLOGY OF CANCER What can cause this? (7th Ed. Ch. 19, pp 370-374) Genes that play a role in normal cell cycle control are altered in some way. 1. Genes that stimulate cell division Normal version of gene: Proto-oncogene -stimulate cell cycle Mutated version: Oncogene- actively promotes cancer. Activates cell division at inappropriate time or place Examples: myc- alters transcripton factor- (brain/blood, lung cancers) PDGF- alters GF or GF receptors (brain cancers) Ras- affects signal transduction (G protein) (lung, colon ovary, pancreas) Breast cancer
2. Tumor Suppressor Genes: Two Classes - Genes involved in blocking cell division (checkpoints) Ex- p53- normally stops cell cycle when DNA is damaged and promotes apoptois if not fixed- found to be mutated in 50% of cancers RB- releases brake on cell cycle- eye, bone breast lung bladder cancers - DNA Repair Genes (fix mutations in DNA) ex: APC- DNA more replication errors (colon & Stomach cancers) hMH2 disrupts DNA mismatch repair (colon, uterus, ovarian cancers)
0ncogene Tumor suppressor p21 (binds cdk)
p27 binds to cyclin and CDK blocking entry into S phase. Breast cancer prognosis is determined by p27 levels. Reduced levels of p27 predict a poor outcome for breast cancer patients.
To develop cancer it takes multiple mutations in the same cell. At least two mutations: One oncogene, one tumor suppressor gene.
Some people are predisposed to getting a particular type of cancer. (Genetic Pre-dispositions) Have ch. 5q mutation - hyperproliferation of epithelium, DNA hypomethylated-> Chromosome 12p (Ras gene)-> Ch 17p (p53 genes- Carcinoma-> more mutations-> metastasis
Metastasis- Cancer invasion Cancer adheres to normal cells that lie next to tissue basement membrane (separates tissues) Secretes substances that cause normal cell to move away Secretes enzymes to penetrate basement membrane Migrates through tissues- lymph
Cancer Treatment Strategies • Surgery • Chemotherapy • Radiation • Blocking hormone receptors • Inducing differentiation • Blocking telomerase activity • Inhibiting angiogenesis • Inducing apoptosis