Cell Cycle Control and Cancer What happens when things go wrong?

Essential Question(s) 1.How does the cell regulate the stages of the cell cycle and what happens when regulation fails?

Cell Cycle Review G2G2 S G1G1 M metaphase prophase anaphase telophase interphase (G 1, S, G 2 phases) mitosis (M) cytokinesis (C) C

Frequency of Cell Division

Turn and Talk 1

Overview of Cell Cycle Controls ENTER MITOSIS homologous chromosomes sister chromatids homologous chromosomes

Turn and Talk 2

How do cells know when to divide?

Internal Cell Cycle Controls

Cdk / G 1 cyclin MPF G2G2 S G1G1 C M G 2 checkpoint APC Active Inactive Active Inactive Active mitosis Cytokinesis MPF = Mitosis Promoting Factor APC = Anaphase Promoting Complex Replication completed DNA integrity Chromosomes attached at metaphase plate M / Spindle checkpoint Growth factors Nutritional state of cell Size of cell Restriction Point

Turn and Talk 3

Cancer

What Causes Cancer?

Loss of Cell Cycle Control in Cancer

Multiple Hit Hypothesis

p53 Tumor Suppressor Gene DNA damage is caused by heat, radiation, or chemicals. p53 allows cells with repaired DNA to divide. Step 1 DNA damage is caused by heat, radiation, or chemicals. Step 1 Step 2 Damaged cells continue to divide. If other damage accumulates, the cell can turn cancerous. Step 3 p53 triggers the destruction of cells damaged beyond repair. ABNORMAL p53 NORMAL p53 abnormal p53 protein cancer cell Step 3 The p53 protein fails to stop cell division and repair DNA. Cell divides without repair to damaged DNA. Cell division stops, and p53 triggers enzymes to repair damaged region. Step 2 DNA repair enzyme p53 protein p53 protein

External Cell Cycle Controls

Tumor Angiogenesis

Tumor Metastasis

Increased Cell Growth in Tumors in vivo

PECAM1 (CD31) 40X dnRBP-J #9pMEXneo

Anchorage Independent Growth in vitro pMEXneosJ1dnRBP-J #1dnRBP-J #9

Tumor Metastasis in vitro PECAM1 (CD31) 10X40X dnRBP-J #9 pMEXneo

Enduring Understandings 1.When a cell specializes, it often enters into a stage where it no longer divides, but it can reenter the cell cycle when given appropriate cues. Non-dividing cells may exit the cell cycle, or hold at a particular stage in the cell cycle. 2.The cell cycle is a complex set of stages that is highly regulated with checkpoints, which determine the ultimate fate of the cell. 3.The cell cycle is directed by internal controls or checkpoints. 4.Cyclins and cyclin-dependent-kinases control the cell cycle. 5.External signals also provide stop-and-go signs at the checkpoints. 6.Cancer results due to disruptions of the cell cycle.