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The size of a tumor first detectable by X-ray: 10 8 cells

A Typical Solid Tumor…. The size of a tumor first detectable by X-ray: 10 8 cells The size of a tumor first palpable: 10 9 cells The size of tumor at death of patient: 10 12 cells. Is Unregulated Cell Division Sufficient To Cause an Increase in Tumor Size??. Growth with

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The size of a tumor first detectable by X-ray: 10 8 cells

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  1. A Typical Solid Tumor… The size of a tumor first detectable by X-ray: 108 cells The size of a tumor first palpable: 109 cells The size of tumor at death of patient: 1012 cells Is Unregulated Cell Division Sufficient To Cause an Increase in Tumor Size??

  2. Growth with No Cell Division Cell Division + Growth = Proliferation! Cell Division No Growth The Difference Between Growth and Cell Division

  3. Growth with No Cell Division: A Differentiated Neuron

  4. Cell Division with No Growth: Early Development OOCYTE GROWS WITHOUT DIVIDING (MONTHS) FERTILIZED EGG DIVIDES WITHOUT GROWING (HOURS) FERTILIZATION 1 mm sperm tadpole feeds, grows and bcecomes an adult frog

  5. A Typical Solid Tumor…Needs to Grow The size of a tumor first detectable by X-ray: 108 cells The size of a tumor first palpable: 109 cells The size of tumor at death of patient: 1012 cells Unregulated Proliferation: Cancer!

  6. Budding Yeast Saccharomyces cerevisiae

  7. Cdc Mutants Affect the Cell Cycle, Not Growth Permissive (low) temperature Restrictive (high) temperature

  8. Cell Division can be Uncoupled From Growth in Drosophila Wild Type: Cdc2 active everywhere Cdc2 inactive in anterior cells Cdc2 active in posterior cells But the overall tissue size is the same as wild type. Weigmann et al., Development 124, 3555-3563 (1997)

  9. Mammalian Cells Growing in Cell Culture 1961Hayflick and Moorhead Showed that human fibroblasts die after a finite number of divisions in culture. This is called “The Hayflick Limit”

  10. Some Commonly Used Cell Lines

  11. Growth Factors Induce Cell Cycle Progression Growth Factors act at the Restriction Point

  12. pm = post mitotic ps = pre-synthetic Zetterberg and Larsson, PNAS 82:5365 (1985)

  13. Growth Factors Induce Gene Expression

  14. Growth Factors Oncogene Expression

  15. Growth Factors Induce Cyclin D1 Expression c-fos is a subunit of AP1! Sherr and McCormick, Cancer Cell, Vol 2, 103-112 (2002)

  16. Cyclin D Expression is Required for S Phase

  17. Cyclin D/cdk4 Controls Growth in Flies Meyer et al., EMBO19: 4533-4542 (2000) Datar et al., EMBO 19: 4543-4554 (2000)

  18. p18 (cycD/cdk4 CKI) Mutation Induces Growth in Mice Franklin et al., Molecular and Cellular Biology, 20: 6147-6158 (2000)

  19. Mitogen Induced Cell Cycle Progression in Cell Culture

  20. Cyclin D as an Oncogene Disease: INVOLVED IN B-LYMPHOCYTIC MALIGNANCY (PARTICULARLY MANTLE-CELL LYMPHOMA) BY A CHROMOSOMAL TRANSLOCATION T(11;14)(Q13;Q32) THAT INVOLVES CCND1 AND IMMUNOGLOBULIN GENE REGIONS (BCL1 ONCOGENE). Disease: INVOLVED IN A SUBSET OF PARATHYROID ADENOMAS BY A CHROMOSOMAL TRANSLOCATIONT(11;11)(Q13;P15) THAT INVOLVES CCND1 AND THE PARATHYROID HORMONE (PTH) ENHANCER (PRAD1 ONCOGENE).

  21. Translocations Cause One Gene to be Controlled by Another

  22. Cancer Cells Display Genetic Instability Examples of genetic instability: 1) gene amplification 2) anueploidy: chromosome gain and loss 3) chromosome rearragements 4) somatic point mutations

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