L11 Abnormal Cell Growth

Objectives

  1. Discuss the role of genes in cancer

  2. Describe the concept of oncogenes and proto-oncogenes

  3. Discuss the concept of tumor suppressors

  4. Discuss the role of oncogenes and tumor suppressor genes in abnormal cell growth



  1. How does cell production achieve homeostasis?

    • equal rate of new cells and cells lost

    • malfunction in this regulatory mechanism → pathological disorders

  2. What can lead to more production of new cells but decreased rate of cell loss?

    • Aging

  3. What are proto-oncogenes or c-onc aka normal/cellular?

    • produces proteins that regulate normal cell growth, functions, and differentiation

  4. What happens when there is a mutation in proto-oncogenes?

    • Qualitative and/or Quantitative changes can form an Oncogene (protein products) or v-onc (mutated/viral) that lead to inappropriate cell proliferation (over-stimulate cell division)

  5. What are the types of mutations/changes → Ontogenesis (functional products)

    • Point Mutation

      • abnormal or excessive proteins

    • Insert Mutation

    • Amplification

      • increased quantity

    • Truncation

    • Chromosomal Translocation

  6. What are onco-proteins

    • proteins produced by oncogenes

  7. What are some oncogenes acronyms

    • Myc — Myelocytomatosis

    • Sis — Simian Sarcoma

    • Erb — Erythroblastoma

    • Src — Rous sarcoma virus

    • Ras — Rat sarcoma

    • Yes — Y73 & ESh sarcoma isolated from Mr. Esh’s chicken

    • Abl — Abelson murine leukemia virus

    • Fos — Finkel biskis jinkins reilly mouse sarcoma

    • jun — junana

  8. What does c-erbB codes for?

    • EGFR

  9. Which erbB is a constitutively activated Receptor Tyrosine Kinases (RTK) and not controlled by the ligand-binding domain to divide?

    • v-erbB

  10. What does v-erbB codes for?

    • abnormal EGFR that lacks a large portion of the N-terminal ligand-binding domain

  11. What transcribed characteristic is seen in v-erbB which can result in a highly aggressive and malignant brain tumor (30%) called Glioblastoma multiforme?

    • Deletion in the EGFR VIII

  12. Is EGFR VIII present in both normal and brain tumor cells?

    • No, it leads to accelerated cell proliferation, invasion, angiogenesis, and metastasis in only brain tumor cells.

  13. Ras Oncogenes has an imbalance of GDP and what that can result in uncontrolled growth, proliferation, and migration → cancer?

    • GTP

  14. What is a rare but highly aggressive and fast growing B-cell non-Hodgkin lymphoma (NHL)?

    • Burkitt’s Lymphoma

  15. In Burkitt’s Lymphoma, the immunoglobulin gene on chromosome 8 is translocated to what on chromosome 14?

    • c-myc gene

  16. In Chronic Myelogenous Leukemia (CML), translocate what two genes between chromosomes 9 and 22?

    • BCR and ABL

  17. What enzyme has revolutionized the treatment of Chronic Myelogenous Leukemia (CML)?

    • Tyrosine Kinase Inhibitors

  18. An increasing number of what cells in the blood and bone marrow indicates Chronic Myelogenous Leukemia (CML)?

    • Myeloblasts

  19. What Oncogene forms when stress, oncoproteins, and/or growth factors lead to the dimer formation between Fos-like and Jun oncogenes?

    • C-fos

  20. What are Tumor Suppressor Genes?

    • Segments of DNA that codes negative regulator proteins

  21. What is the function of a Tumor Suppressor Gene?

    • Reduces the probability of a cell in a multicellular organism → tumor cell by stopping uncontrolled cell division cycle

  22. What can happen to a Tumor Suppressor Gene for it to INCREASE the chance of tumor formation?

    • Mutation or Deletion in the gene

  23. What are examples of Tumor Suppressor Genes?

    • P53, Rb, PTEN, BRCA -1 and -2

  24. What was the first ever Tumor Suppressor Gene to be discovered in Human Retinoblastoma?

    • pRb

  25. How does the Rb gene function?

    • pRb is bound with E2F until it undergoes phosphorylation via Cyclin activation

    • E2F is released to continue cell division

  26. T/F: p53 can only stop in one phase of the cell cycle

    • False, it can stop in multiple places

  27. List the factors that can activate p53

    • Lack of Nucleotides

    • UV Radiation

    • Ionizing Radiation

    • Oncogene Signaling

    • Hypoxia

    • Blockage of Transcription

  28. When p53 is inactive, it forms a dimer with what?

    • mdm2

  29. What are the functions of p53 after sensing DNA damage?

    • induce G1 arrest via p21

    • induce DNA repair

    • induce apoptosis

  30. What is p53’s nickname

    • Guardian of the Genome

  31. What happens when p53 is impaired

    • accumulation of damaged DNA → malignancy

  32. The homozygous loss of p53 is seen in which type of cancers?

    • All

  33. T/F: loss of p53 is only seen in cancerous cells

    • False, it is seen if over half of malignant cells

  34. Describe the pathway of Colon CA development

    1. Normal epithelium experiences loss of APC, tumor suppressor gene

    2. Polyp of small benign growth forms which can activate KRAS oncogene

    3. Early Adenoma with a large benign growth can lose DCC, tumor suppressor gene

    4. Late Adenoma can lose p53 and form a Carcinoma or malignant tumor → colon cancer and metastasis with additional mutations

  35. Inherited Mutations and CA