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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
Figure 12.3 Chromosome duplication and distribution during mitosis
Figure 12.0 Mitosis
The functions of Mitotic cell division: 1.) Reproduction
Asexual reproduction of a unicellular, eukaryotic organism
2.) Development
3.) Tissue renewal in adults
Figure 12.4 The cell cycle
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.
Figure 12.6 The mitotic spindle at metaphase
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
Figure 12-09x Mitosis in an onion root
Figure 12.11 A hypothesis for the evolution of mitosis
Evidence for cytoplasmic chemical signals in cell cycle regulation
Regulation of the Cell Cycle
Mechanical analogy for the cell cycle control system
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
Fibroblast growth
-Density-dependent inhibition
-Anchorage dependence
Density-dependent inhibition of cell division
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)
Breast cancer
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)
p21 (binds cdk)
0ncogene
Tumor suppressor
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 invasion1. Cancer adheres to normal cells that
lie next to tissue basement membrane (separates tissues)
2. Secretes substances that cause normal cell to move away
3. Secretes enzymes to penetrate basement membrane
4. Migrates through tissues- lymph
Cancer Treatment Strategies
• Surgery
• Chemotherapy
• Radiation
• Blocking hormone receptors
• Inducing differentiation
• Blocking telomerase activity
• Inhibiting angiogenesis
• Inducing apoptosis