A Presentation From the American Cancer Society Cancer Statistics 2005 A Presentation From the American Cancer Society The American Cancer Society presents Cancer Statistics 2005. ©2005, American Cancer Society, Inc.

US Mortality, 2002 No. of deaths % of all deaths Rank Cause of Death 1. Heart Diseases 696,947 28.5 2. Cancer 557,271 22.8 3. Cerebrovascular diseases 162,672 6.7 4. Chronic lower respiratory diseases 124,816 5.1 5. Accidents (Unintentional injuries) 106,742 4.4 6. Diabetes mellitus 73,249 3.0 7. Influenza and pneumonia 65,681 2.7 8. Alzheimer disease 58,866 2.4 9. Nephritis 40,974 1.7 10. Septicemia 33,865 1.4 Cancer accounts for nearly one-quarter of deaths in the United States, exceeded only by heart diseases. In 2002, there were 557,271 cancer deaths in the US. Source: US Mortality Public Use Data Tape 2002, National Center for Health Statistics, Centers for Disease Control and Prevention, 2004.

Change in the US Death Rates* by Cause, 1950 & 2002 Rate Per 100,000 1950 2002 Compared to the rate in 1950, the cancer death rate was about the same in 2002, while rates for other major chronic diseases decreased during this period. Heart Diseases Cerebrovascular Diseases Pneumonia/ Influenza Cancer * Age-adjusted to 2000 US standard population. Sources: 1950 Mortality Data - CDC/NCHS, NVSS, Mortality Revised. 2002 Mortality Data: US Mortality Public Use Data Tape, 2002, NCHS, Centers for Disease Control and Prevention, 2004

The Hallmarks of Cancer Hanahan and Weinberg, Cell 100:57-70 (2000)

Cell Regulatory Networks Important in Cancer Cells Hanahan and Weinberg, Cell 100:57-70 (2000)

The Cell Cycle START or Restriction Point

The Main Jobs of the Cell Cycle: To accurately transmit the genetic information! To maintain normal ploidy; i.e. diploidy! Euploidy: additions of whole chromosome sets e.g. n, 2n, 3n, 4n = haploid, diploid, triploid, tetraploid Aneuploidy: additions or subtractions of one or more single chromosomes e.g. 2n + 1, 2n -1, 2n + 2, etc.

Properties Required for Transmission of Chromosomes During Cell Division 1. One and only one centromere 2. Functional telomere at both ends 3. Chromosomes must be fully replicated 4. Chromosomes cannot be too large or too small

S Phase of the Cell Cycle

Mitosis

Fibroblasts in Culture blue = DNA green = microtubules

Mitosis in an Early Fruit Fly Embryo

Anaphase in a plant cell

Metaphase in a mammalian cell

G1-S and G2-M are the major control points in the cell cycle Fuse M phase cell with interphase cell: Interphase nucleus enters M Fuse S phase cell with G1 cell: The G1 nucleus enters S phase Fuse S phase cell with G2 cell: The G2 nucleus does not enter S phase Rao and Johnson cell fusion experiments

Cyclin Dependent Kinases Regulate the Cell Cycle

Experimental Systems Important for Cell Cycle Studies Saccharomyces cerevisiae Arbacia punctulata Schizosaccharomyces pombe Xenopus laevis

Fission yeast: Schizosaccharomyces pombe

Budding Yeast Saccharomyces cerevisiae

Isolating Temperature Sensitive Mutants in Haploid Yeast

Cdc Mutants Arrest at the Same Cell Cycle Phase Permissive (low) temperature Restrictive (high) temperature

Phosphorylation of CDK Targets Changes Their Activity Now performs a cell cycle function

The Behavior of a Temperature Sensitive cdc Mutant cdc mutant growing at permissive temp (23C) cdc mutant growth arrested after 6 hrs at non-permissive temp (36C)

How to Clone cdc Genes in Yeast

Cdc Genes Encode Proteins Needed for DNA Replication Studies in S. cerevisiae

Cdc Genes Encode Proteins Needed for the G2-M Transition: Studies in S. pombe cdc2+ encodes a kinase Moreover = cdc28 in S. cerevisiae!

Cyclin was Discovered in Sea Urchin Embryos can stimulate to lay lots of eggs Protein Level Time cyclin A cyclin B M

(Spisula is actually a clam.) mitosis (Spisula is actually a clam.)

Overview of the frog life cycle OOCYTE GROWS WITHOUT DIVIDING (MONTHS) FERTILIZED EGG DIVIDES WITHOUT GROWING (HOURS) FERTILIZATION 1 mm sperm tadpole feeds, grows and bcecomes an adult frog

The Maturation of Frog Eggs

The Maturation of Frog Eggs An Assay for Maturation Promoting Factor (MPF) Yoshio Masui, 1971

MPF Activity Peaks Before Each Cell Division Moreover, MPF has kinase activity

Purification of MPF: The Birth of Cyclin Dependent Kinases This is cdc2+!! (Cdc28 in S. cerevisiae) This is cyclin!! Which = cdc13+ in S. pombe

Phosphorylation of CDK Targets Changes Their Activity Now performs a cell cycle function

The Nobel Prize in Physiology or Medicine, 2001 “for their discovery of key regulators of the cell cycle”