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A cancer is an uncontrolled proliferation of cells
• Failure in the mechanisms by which the cell cycle is regulated can lead to uncontrolled cell growth and the development of cancer • In some the rate is fast; in others, slow; but in all cancers the cells never stop dividing. • Cancer cells are usually less differentiated than the normal cells of the tissue where they arose.

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Cell Cycle • The repeating sequence of growth and division through which cells pass each generation • The purpose of the cell cycle is to allow cells to reproduce without alteration of genetic material • The stages are well preserved between species Free Powerpoint Templates Page 5 .

Why do cells devide? Free Powerpoint Templates Page 6 .

Events of cell cycle • G1 =Growth and preparation of the chromosomes for replication • S = Synthesis of DNA • G2 = Preparation for mitosis • M = Mitosis Periode between M and S is called G1. between S and M is G2 Free Powerpoint Templates Page 7 .

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Cell cycle progression • Higly regulated process controlled by a large number of factors include: – Growth stimulating factors – Growth inhibiting factors – Enzymes that alter functional state of other proteins by adding (kinases) or removing (phosphatases) phosphate groups • Failure in the mechanisms by which the cell cycle is regulated can lead to uncontrolled cell growth and the development of cancer Free Powerpoint Templates Page 12 .

a gene mutation occurs. the DNA is checked to make sure it has replicated correctly. Before a cell divides. (If DNA does not copy itself correctly. Free Powerpoint Templates Page 13 .Control of Cell Cycle There are several factors that regulate the cell There are several factors that regulate the There are severala cell divides regulate the cycle and assure factors that correctly cell cycle and assure a cell divides correctly cell cycle and assure a cell divides correctly 1.

Control of Cell Cycle There are several factors that regulate the There are several factors that regulate the There are several factors that regulate the cell cycle and assure a cell divides correctly cell cycle and assure a cell divides correctly cell cycle and assure a cell divides correctly 2. Chemical Signals tell a cell when to start and stop dividing Free Powerpoint Templates Page 14 .

Control of Cell Cycle • There are important checkpoints during the cell cycle: – At the G1 – S transition – At the S – G2 transition – At the G2 – M transition • Regulation of the cell cycle occurs as a consequence of cyclin – Cdk interaction • Other proteins such as P53. Rb and oncogene play a role in regulating the cell cycle Free Powerpoint Templates Page 15 .

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6 Cdk 2 Cdk 2 Cdk 1(Cdc2) Cdk 1 Process regulated G1 phase progression G1 to S phase S phase progression S through G2 M phase Free Powerpoint Templates Page 17 .Cyclins and Cyclin Dependent Kinases (Cdk) Cyclin Cyclin D Cyclin E Cyclin A Cyclin A Cyclin B Cdk Cdk 4.

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Waves of Cyclin-Cdk Activity Control The Cell Cycle G1 S G2 M G1 Cyclin B-Cdk1 Kinase Activity CyclinA-Cdk1 Cyclin E-Cdk 2 Cyclin D-Cdk 4/6 Time GF .

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S and M • Checkpoint signals – report cell’s status: – Is the cell big enough? – Is environment favorable? – Is DNA replicated? – Are chromosomes attached poles? Free Powerpoint Templates to opposite Page 22 .Checkpoints • The cell cycle control system has checkpoints during G1. G2.

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G1 S G2 prophase metaphase anaphase Cytokinesis Mitosis .

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Haemopoietic Liver. Cardiac muscle • Permanent Free Powerpoint Templates Page 26 .Regenerative Capacity • Labile • Stable Epithelial. Lymphoid. Salivary gland. Skeletal muscle. Pancreas. Endocrine organs Neurons.

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Cell proliferation and cancer • It was originally assumed that cancer arose from a population of cells that proliferated more rapidly than normal cells • It is now known that many malignant cells have longer cell cycle times than their normal counterparts Free Powerpoint Templates Page 29 .

What happens in malignancy? • Malignancies probably arise when there is an imbalance between cell production and cell loss • Cell loss occurred through necrosis. apoptosis and surface shedding • Abnormalities of the cell cycle do not explain all of the growth of malignant tumors and they are clearly not important in invasion and metastasis Free Powerpoint Templates Page 30 .

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Cell Cycle Is Regulated by Opposing Effects of Positive and Negative Factors S Cyclin + Cdk P53 G2 M G1 Rb Free Powerpoint Templates Page 32 .

BRCA1) Cell proliferation Free Powerpoint Templates Page 33 . Rb) Oncogene (BCl2.BRCA1) Cell proliferation Cell death Tumor Suppressor (P53.Cell Cycle Is Regulated By Opposing Effects of Positive and Negative Factors Tumor Suppressor (P53. Rb) Cell death Oncogene (BCl2.

there is time to live and a time to die • There are two ways in which cells die: – They are killed by injuries agents – They are induced to commit suicide (apoptosis or Programmed cell death.PCD) • Two forms of cell death – Necrosis – Apoptosis Free Powerpoint Templates Page 34 .APOPTOSIS • For every cell.

• Inflammation of surrounding tissues Free Powerpoint Templates Page 35 . such as by: • Mechanical damage • Exposure to toxic chemicals Undergo a characteristic series of changes: • They are swell • The cell contents leak out. leading to.Death by Injury Cells that are damaged by injury.

fragment Free Powerpoint Templates Page 36 .Death by Suicide (Apoptosis) Cells that are induced to commit suicide: • Shrink • Have their mitochondrial break down • Develop bubble-like blebs on their surface • Have the chromatin in their nucleus degraded and show chromatin condensation • Break into small. membrane-wrapped.

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Apoptosis Versus Necrosis Apoptosis • Central part of normal development • Genetically mediated • Involve in organogenesis. tissue homeostasis Necrosis • Results from cell metabolic collapse • Response to injury or toxic damage Free Powerpoint Templates Page 38 .

Apoptosis Versus Necrosis Apoptosis • Shrinkage of cell • Little or no swelling of mitochondria • Intact membrane • Degradation of DNA into multiple of 180 bp • Little or no inflammatory response Necrosis • Swelling of cell • Swelling of mitochondria • Loss of membrane integrity • Random degradation of DNA • Intense inflammatory response Page 39 Free Powerpoint Templates .

Why Should a Cell Commit Suicide? There are two different reasons • Apoptosis is needed for proper development – The formation of the fingers and the toes of the fetus requires the removal. by apoptosis of the tissue between them • Apoptosis is needed to destroy cells that represent a thread to integrity of the organism – Cells infected with viruses – Cells of the immune system – Cells with DNA damage Free Powerpoint Templates Page 40 .

tumor suppressor) Free Powerpoint Templates Page 41 . oncogenes) • The receipt of negative signals (increased levels of oxidant damage of DNA.What Makes Cell Decide to Commit Suicide? The balance between: • The withdrawal of positive signals. cytokines. signal needed for continued survival (GF. that is.

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