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Concept 12.3 The cell cycle is driven by specific chemical signals that act as controls Internal controls – mostly in the cytoplasm External controls – from an outside source Events of the cell cycle are directed by a distinct cell cycle control system driven by a built in clock - timing regulated at certain checkpoints 12.3 – 3 major checkpoints For most cells, the G1 checkpoint seems to be the most important one Cell receives a go-ahead signal at the G1 checkpoint, it will usually complete the S, G2, and M phases and divide Cell does not receive the go-ahead signal, it will exit the cycle, switching into a non-dividing state called the G0 phase A lot of cells found in G0 Fig. 12-15 G0 G1 checkpoint G1 (a) Cell receives a go-ahead signal G1 (b) Cell does not receive a go-ahead signal Signal molecules in cell cycle The activity of cyclins and Cdks fluctuates during the cell cycle Cdks (cyclin dependent kinases) are present inside the cell in constant concentration and inactive Cyclins build up in the cell during certain phases and activate Cdks Cyclins activate Cdks When cells are dividing Cdk activity (not concentration) lowers; waiting for the concentration of cyclins to build again Fig. 12-16 RESULTS 5 30 4 20 3 2 10 1 0 100 200 300 Time (min) 400 0 500 When a cyclin and Cdk bind they form a cyclinCdk complex Ex: MPF (M phase-promoting factor) triggers a cell’s passage past the G2 checkpoint into the M phase Highest levels of MPF are when a cell goes into mitosis Fig. 12-17 M S G1 G2 M G1 S G2 M G1 MPF activity Cyclin concentration Time (a) Fluctuation of MPF activity and cyclin concentration during the cell cycle Degraded cyclin G2 checkpoint Cyclin is degraded MPF Cdk Cyclin (b) Molecular mechanisms that help regulate the cell cycle Cyclin accumulation Cdk Other Internal and External Signals internal signals - kinetochores not attached to spindle fibers correctly in metaphase delays anaphase external signals - growth factors, proteins released by certain cells that stimulate other cells to divide platelet-derived growth factor (PDGF) stimulates the division of human fibroblast cells in culture – make collagen a connective tissue Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Fig. 12-18 Scalpels Petri plate Without PDGF cells fail to divide With PDGF cells proliferate Cultured fibroblasts 10 µm external signal - is density-dependent inhibition, in which crowded cells stop dividing If part of sample removed, signal to bordering cells to divide to fill in the gap external signal - anchorage dependence, in which they must be attached to a substrate in order to divide Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Fig. 12-19 Anchorage dependence Density-dependent inhibition Density-dependent inhibition 25 µm 25 µm (a) Normal mammalian cells (b) Cancer cells Cancer cells ignore signals to stop dividing have escaped from normal cell cycle controls and external signals they do not respond to the control mechanisms – anchorage dependence, density dependent inhibition, or checkpoints if cancer cells stop dividing, it is at random points and not at the checkpoints They even secret their own growth factors – will ignore healthy normal cell growth factors Cancer cells… Form when a normal cell undergoes a transformation – becomes cancer cell no longer responding to control mechanisms- would normally be destroyed by immune system if the cell evades destruction by the immune system it may form a tumor – mass of abnormal cells Tumors… remain at the original site, it is called a benign tumor becomes invasive enough to impair the functions of surrounding tissue and organs now have a malignant tumor cells spread from the original site is called metastasis Cells spread through blood stream and lymphatic system Fig. 12-20 Lymph vessel Tumor Blood vessel Cancer cell Metastatic tumor Glandular tissue 1 A tumor grows from a single cancer cell. 2 Cancer cells invade neighboring tissue. 3 Cancer cells spread to other parts of the body. 4 Cancer cells may survive and establish a new tumor in another part of the body. Concept 12.3 Treating cancer… Localized tumors are treated through high does of radiation Metastasized tumors are treated with chemotherapy – combo of toxic drugs Both treatments also affect healthy cells that rapidly divide Hair cells GI tract – mouth, esophagus, stomach lining
