Mitosis and Cancer

1. Mitosis and Cancer PART 3 Honors Genetics Ms. Gaynor

2. Another Type of Cell Division: Binary Fission • Prokaryotes (bacteria) • Reproduce by a type of cell division called binary fission

3. Origin of replication Cell wall Plasma Membrane E. coli cell Bacterial Chromosome Chromosome replication begins. Soon thereafter, one copy of the origin moves rapidly toward the other end of the cell. Two copies of origin 1 Replication continues. One copy ofthe origin is now at each end of the cell. 2 Origin Origin Replication finishes. The plasma membrane grows inward, and new cell wall is deposited. 3 4 Two daughter cells result. • In binary fission, • The bacterial chromosome replicates • The two daughter chromosomes move apart Figure 12.11

4. The cell cycle is HIGHLY regulated • The frequency of cell division • Varies with the type of cell • These cell cycle differences • Result from regulation at the molecular level • http://highered.mcgraw-hill.com/sites/0072495855/student_view0/chapter2/animation__how_the_cell_cycle_works.html

5. Cell Cycle Checkpoints • The clock has specific checkpoints • a critical control point where stop and “go-ahead” signals can regulate cycle • These signals report whether crucial cellular processes up to that specific point have been completed and completed correctly • There are 3 checkpoints • G1 checkpoint • G2 Checkpoint • M checkpoint • spindle assembly checkpoint

6. G1 checkpoint Control system S G1 G2 M M checkpoint Figure 12.14 G2 checkpoint The Cell Cycle Control System • The sequential events of the cell cycle • Are directed by a distinct cell cycle control system, which is similar to a clock

7. G0 G1 checkpoint G1 G1 If a cell does not receive a go-ahead signal at the G1checkpoint, cell exits the cell cycle and goes into G0, a nondividing state. If a cell receives a go-ahead signal at the G1 checkpoint, the cell continues on in cell cycle. Figure 12.15 A, B G1 Checkpoint

8. G1 Checkpoint • Restriction point just before entry into S phase • Checks cell size & original DNA for damage • Makes key decisions  should cell divide or delay division and enter G0 (resting) phase • Most cells stop at this stage and enter a resting state called G0

9. G2 Checkpoint • Checks cell size • Triggers start of M phase • DNA is frequently damaged prior to mitosis  if this happens, the cell cycle is arrested via inactivation of cell cycle “control” proteins

10. M Checkpoint • Makes sure spindle assembly is correct • Makes sure all chromosomes are aligned at the mitotic plate

12. The Cell Cycle Clock: Cyclins and Cyclin-Dependent Kinases • Two types of regulatory proteins in cytoplasm are involved in cell cycle control • Cyclins • Cyclin-dependent kinases (Cdks)

13. INACTIVE FORM CYCLIN DEPENDENT KINASE (CDK) CYCLIN + ACTIVE FORM CDK/CYCLIN COMPLEX

14. Active vs. Inactive?? • What happens when cyclins and cdks are in the ACTIVE form? • Cells can pass through the cell cycle to the NEXT phase  • What happens when cyclins and cdks are in the INACTIVE form? • Cells can NOT pass through the cell cycle to the NEXT phase 

15. cyclin degrades & breaks apart cyclin degrades & breaks apart

16. What degrades (breaks down) cyclins? • Proteolytic enzymes (proteins) • Break down/degrade cyclins  cause them to fluctuate in [ ] • “PROTEO” means protein • “LYTIC” means break or lyse REMEMBER: • Cyclin concentration fluctuates (changes) • Cdk concentration stays the SAME

17. Important Cyclins and CDKs Cyclin D-CDK4 Cyclin E-CDK2 Cyclin A-CDK2 Cyclin B-CDC2

18. Control of Cell Cycle Animations • http://highered.mcgraw-hill.com/sites/0072495855/student_view0/chapter2/animation__control_of_the_cell_cycle.html • Amination #8 http://www.cellsalive.com/apop.htm

19. 2 µm Figure 21.17 Programmed Cell Death (Apoptosis) • In apoptosis • http://www.biooncology.com/bioonc/research/apoptosis/index.m • Cell signaling is involved in programmed cell death needed to maintain healthy tissues/ cell function

20. Stop and Go Signs: Internal and External Signals at the Checkpoints • Both internal (inside the cell) and external (outside the cell) signals • Control the cell cycle checkpoints

21. Internal and External Signals • Internal signals • DNA synthesis • Growth/Nutrition • CDK/Cyclins • External signals • Growth factors & Hormones • Density Dependent Inhibition • Anchorage Dependence

22. Influences on Cell Division • Growth factors & hormones • Stimulate other cells to divide • In density-dependent inhibition • Crowded cells stop dividing • Most animal cells exhibit anchorage dependence • In which they must be attached to a structure to divide • Ex: extracellular matrix of a tissue

23. (a) Cells anchor to dish surface and divide (anchorage dependence). When cells have formed a complete single layer, they stop dividing (density-dependent inhibition). Normal mammalian cells. **The availability of nutrients, growth factors, and a substratum for attachment limits cell density to a single layer. If some cells are scraped away, the remaining cells divide to fill the gap and then stop (density-dependent inhibition). Figure 12.18 A 25 µm

24. Cancer cells usually continue to divide well beyond a single layer, forming a clump of overlapping cells. Figure 12.18 B 25 µm Cancer cells • Exhibit neither density-dependent inhibition nor anchorage dependence • Immortal cells (if enough nutrients)

25. Loss of Cell Cycle Controls in Cancer Cells • Cancer cells • Do not respond normally to the body’s control mechanisms • Form tumors • TUMOR= mass or group of abnormal dividing cells

26. Why? • Don’t need growth factors  maybe they make their own growth factors • Mutations in GENES!!! • Ex: cyclin or Cdk genes

27. Loss of Cell Cycle Controls in Cancer Cells • Cancer cells • Normal cell  cancer cells using process of transformation • Form tumors • Benign “fine” • Clump of cells remain at orginal spot • Malignant “mean” “cancer” • Loose/destroy attachments to other cells  they can spread!!!

28. Malignant tumors • These tumors invade surrounding tissues and can metastasize • Exporting cancer cells to other parts of the body where they may form secondary tumors • USE BLOOD STREAM and LYMPH VESSELS TO SPREAD!!! • http://www.hhmi.org/biointeractive/media/angiogenesis-lg.mov

29. 3 4 1 2 Tumor Lymphvessel Bloodvessel Glandular tissue Cancer cell MetastaticTumor Cancer cells spread through lymph and blood vessels to other parts of the body. A small percentage of cancer cells may survive and establish a new tumor in another part of the body. A tumor grows from a single cancer cell. Cancer cells invade neighboring tissue. Figure 12.19

30. Cancer Treatment • Radiation destroys DNA in cancer cells (these cells have lost ability to repair damage) • Chemotherapeutic drugs interfere with specific steps in cell cycle • Also effects normal cells 

31. Cancer Causing Agents • Genetics (inherited) • Spontaneous mutation • Envinromental Mutagens (a.k.a- carcinogen) • Sun • Viruses • Chemicals

32. Cancer Animations- REVIEW Cancer Movie • http://www.cancerquest.org/index.cfm?page=3102&lang=english • http://science.education.nih.gov/supplements/nih1/cancer/activities/activity2_animations.htm

33. Flashcard Vocabulary • http://highered.mcgraw-hill.com/sites/0078757150/student_view0/vocabulary_eflashcards.html