1 / 61

Chapter 16- Cancer

Chapter 16- Cancer. Where we’re going Characteristics of cancer cells Some names Convince you that cancer is a result of multiple genetic defects Molecular genetics of cancer We’ll be connecting cancer to growth and signaling. A few treatments. Why this is important.

pleasance
Download Presentation

Chapter 16- Cancer

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. Chapter 16- Cancer Where we’re going • Characteristics of cancer cells • Some names • Convince you that cancer is a result of multiple genetic defects • Molecular genetics of cancer • We’ll be connecting cancer to growth and signaling. • A few treatments

  2. Why this is important • About 1 in 4 of us get cancer, 1 in 5 die of it- at least. • It’s very much a disease that can be understood at the molecular level. • Our understanding has not resulted in the cures we’d like

  3. No particular relevance- painted by Van Gogh in the 1880’s!

  4. Cancers vary in terms of getting a type of cancer and dying from that type Data 2000-2003

  5. Basic Properties of cancer cells • Uncontrolled- grow at the usual rate, but then keep growing when other cells would normally stop- ignore stopping signals, or grow w/o added signals. • Invasive • Immortal- normal cells undergo senescence- telomerase is 1 factor. • Chromosomal abnormalities- aneuploid

  6. Well-behaved- stop growing when they cover the dish.

  7. Not well-behaved- keep growing after they cover the dish.

  8. Internal signals allow serum-free growth

  9. Names: • A. tumor/neoplasm: clone of cells capable of uncontrolled growth; • benign: contained • malignant: spreading • B. classified by tissue of origin: • carcinoma-epithelial tissue • sarcoma- mesodermal origin: muscles, connective tissue, vascular tissue • leukemia/lymphoma- blood forming (hemopoietic) cells

  10. Origins of cancer cells • Clonal, but highly mutable • Chronic myelogenous leukemia-translocation from 22 to 9 (Philadelphia chromosome)

  11. More than one defect: • 1016 cell divisions in a lifetime; • even at a mutation rate of 1/106, we'd have 1010 mutations in every gene! Thus, it may take 3--7 events, in the same cell, to make it cancerous. evidence:

  12. 1. frequency of cancer, peryear, goes up with age- accumulated mutations. Molecular evidence agrees with this. • http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mboc4.figgrp.4270 Colon cancer of women in England & Wales

  13. 2. tumor progression: e.g., cervical carcinoma: the cells can be in a precancerous stage; undifferentiated; some may be immortal; yet not be cancerous. Only a fraction of the precancerous cells become cancerous. Thus, the changes are typically sequential, rather than having to be simultaneous. Very much an evolutionary event!

  14. Normal- small nuclei

  15. Precancerous- carcinoma in situ

  16. The initiator is mutagenic, while the promoter stimulates growth- the mutant population increases, increasing the likelihood of further mutations • 3. Initiator/promoter studies: Fig. 23-19, MBOC: • http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mboc4.figgrp.4300 • Many cells revert to a less differentiated stage- carcinoembryonic antigen is expressed in embryos, and also in cancers.

  17. 4. Molecular evidence: With the advent of cloned oncogenes, it's been possible to add such genes to normal cells or animals, and determine the results. a. 3T3 cells- already abnormal; single added oncogene makes them cancerous. b. normal cells require two oncogenes: myc & ras both result in transformation. Same results with transgenic mice. 23-30 http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mboc4.figgrp.4325 These are mice with transgenic, overexpressed oncogenes.

  18. A typical progression of cancer

  19. So what causes all those mutations? • Life • Maybe mutagens • Viruses in some cases • Diet can have an effect

  20. However, correlation doesn’t necessarily mean causation…

  21. How are cancer cells different in gene expression? • We can use microarrays to find out! • 1000’s of gene-specific sequences. • Isolate mRNA from cell, turn into cDNA • Hybridize to sequences • Can quantify amounts.

  22. ALL- lymphoid- lymphocytes AML: myeloid- granulocytes, macrophages, dendritic cells

  23. Sometimes this helps- or not

  24. IV. Molecular genetics of cancer: Two basic effects that genes can have on cell growth; • A. stimulate growth: oncogenes; genes that are normally turned on as part of growth, now unusually active. Dominant mutations; also DNA tumor virus genes. • B. inhibit excessive growth: some genes seem to be there to keep oncogenes in line; these mutations tend to be recessive. Tumor suppressor genes, • Cell fusion studies can differentiate between these- Suppressors are recessive to normal, and oncogenes are often dominant over normal.

  25. C. types of stimulatory genes: • 1. DNA tumor virus genes: non-permissive infections result in excessive growth: human viruses infecting hamsters. The virus produces a protein that, in one case binds and inactivates two of the major tumor suppressor genes- Rb and p53, thus allowing uncontrolled DNA replication. (Fig 23-35) • http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mboc4.figgrp.4334

  26. Oncogenes: most were discovered in RNA tumor viruses: carried by certain tumor viruses. We have homologous genes- proto-oncogenes. Types- Cell signaling (RAS), cell regulating, growth factors, GF receptors, transcription factors, anti-apoptosis proteins.

  27. With more changes…

  28. Ways to become a bad oncogene

  29. New copy, overexpressed, comes in from retrovirus! Retrovirus activates, by insertion, nearby proto-oncogene!

  30. These are all oncogenes

  31. Tumor suppressor genes • Tend to halt unregulated cell growth-cell cycle control w/ damage, or inappropriate signals. • Need TWO bad copies before problems occur- recessive.

  32. With further mutations

  33. Retinoblastoma gene- hereditary cancer w/ 90% penetration- born w/ 1 bad copy. It normally is stopping S phase. E2F is major TF, turns on many genes.

  34. P53- the guardian of the genome!! • Transcription factor • Made but unstable • DNA damage (ATM-> CHK2->phosphorylated/stable) • P21 transcribed- binds CDK/Cyclin, stops G1-S transition. • Activates apoptotic genes as well

More Related