Week 3 Flashcards

1
Q

What is oncogenes and causes of it?

A

-mutated gene, has the potential to cause cancer

Cause of oncogene:

  • Virus
  • Chemicals
  • Radiation
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2
Q

Explain what the Rous Sarcoma Virus is

A

It is a retrovirus ( any of a group of RNA viruses which insert a DNA copy of their genome into the host cell in order to replicate)

Gene v-src

  • Involved in regulation of cell growth and differentiation
  • Not needed for viral replication, but transforms cell leading to cancer

Something in the DNA inserted by the Rous sarcoma virus made the host cells cancerous, but what was it?

  • virus picked up a passenger gene called V-src
  • V-src was unmistakably similar, but not identical to a gene- C-src- that was discovered in the normal vertebrate genome. C-src had evidently been caught up accidentally by the retrovirus from the genome of a previously infected hostcell, and it had undergone mutation in the process to become an oncogene (V-src)

V-src oncogene
Virus v-src (oncogene, mutated)
- V-src is dominant= only need one copy
- Gain of function

V-src constitutively active tyrosine kinase
- Signalling molecule
- Cannot be regulated
○ Activates kinase signalling cascades
○ Decreased adhesion of cell to surface
○ Growth to high density
○ Loss of contact inhibition
○ Increased transport of metabolites
- Triggers uncontrolled growth
- Original proto-oncogene from vertebrates, cellular src (c-src)
○ C-src expression activated in human tumours

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3
Q

Explain Avian Leukosis virus

A

Cancer caused by a different mechanism from Rous
- Oncogene

Inserts viral DNA into host genome next to a proto-oncogene
- C-myc (DNA- binding protein) > transcription factor

Viral DNA
- Long tandem repeat sequences
○ Act as strong promoters or enhancers
○ Induces increased expression of c-myc

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4
Q

Receptors

What receptor and function?

A

Receptor Tyrosine kinases (RTKs)
- Receptors for growth factors
○ Transmembrane protein, intra- and extra-cellular domains
○ Signal transduction pathway
○ May be defective in cancers
§ Mutations can result in continually active receptors
§ i.e. Receptor activity in absence of ligand

Defective receptor tyrosine kinases:
- Erb-B family
○ Her2 (aka ErbB2= 25% of breast tumors)

Function

  • Tyrosine kinase domains
  • Binding of ligand > phosphorylation of tyrosine
    ○ Phosphorylate other intracellular signalling proteins
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5
Q

What is Erb-B

A
  • Family of receptor tyrosine kinases related to epidermal growth factor receptor
    ○ Name derived from viral oncogene: erthyroblastic leukemia viral oncogene
  • When extracellular domain is missing
    ○ Receptor is always switch on….
    = Uncontrolled growth
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6
Q

What is P53 (tumour suppressor)

A
  • Regulates cell cycle
  • Activates other transcription factors
  • DNA binding site
  • Recognises DNA damage
  • “Guardian of the genome”
  • can trigger growth arrest, DNA repair, or apoptosis
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7
Q

APC protein ( Adenomatous polyposis coli)

A
  • Tumour supressor protein
  • Inhibits myc gene expression
  • Myc protein (transcription factor)
    Induces expression of many genes required for cell to progress from G1 to S phase
  • Degradation of beta-catenin
  • Beta catenin has 2 roles
  • Cell-cell adhesion
  • Drives transcription of target genes involved in cell proliferation
  • Mutations that activate beta-catenin found in many cancers (oncogene)

APC mutations also cause cancer
- No control of myc or beta-catenin

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8
Q

Colorectal cancer

A
  • Slow developing (over 10-35 years)
  • Pre- cancerous growths
  • Polyps - form on the inside of colon wall
  • Cells in polyp contain mutations in APC gene
  • If cells in polyp undergo mutation in Ras
  • More uncontrolled cell division
  • Another mutation occurs in p53
    Malignant carcinoma

three mutations required

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9
Q

Colorectal cancer

A
  • Inherit mutation in one APC gene (Familial adenomatous polyposis)
    • Only one more mutation= formation of polyps
    • Hereditary disposition to colonic cancer
      • 10% cancer patients
      • Develop cancer at an early age
    • Other patients acquire 2 mutations during their life
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10
Q

Skin

A
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11
Q

Two types of skin cancer

A
  • Melanoma of the skin
    • Starts in melanocytes
  • Non-melanoma skin cancer
    • Basal cell carcinoma (BCC) and squamous cell carcinoma
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12
Q

Non-melanoma skin cancer (NMSC)

Basal cell carcinoma

A
  • Most often found on head, neck and arms
    • Due to exposure to UV radiation
    • Leads to formation of thymine dimers, a form of DNA damage
  • Basal cells invade the dermis
  • Slow growing, usually do not spread
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13
Q

Non-melanoma skin cancer (NMSC)

Squamous cell carcinoma

A
  • Scaly red patches, open sores, warts or elevated growths with a central depression; they may crust or bleed
  • Mostly found on head, neck and arms
  • Fast growing can spread
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14
Q

Diagnosis

A

Asymmetry, irregular

Boards (uneven)

Colour ( variegated)

Diameter (greater than 6mm)

Evolving (changing, growing over time)

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15
Q

Characteristics of cancer cells

A
  • Grow continuously
    • Lack of control, increased rate
  • De-differentiated
    • Loss of specialised function
  • Lack contact inhibition
  • Altered cell surface characteristics
    • Less adhesive
    • Invade other tissues
  • Metastasis
    • Break through basal lamina and enter circulation
    • Secrete a protease > digests basal lamina
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16
Q

Metastasis

A
  • Development of secondary malignant growths at a distance from a primary site of cancer (via blood supply)
    • Reduced cell to cell adhesion and cell-matrix adhesion molecules
  • Mechanism of metastasis
    • If cell-cell or cell-matrix contacts are disrupted
    • Tumour cells degrade extracellular matrix and then get between endothelial cells and into capillary
    • Cancer cells secrete proteases to digest matrix and establish themselves at new site
    • Selectins on endothelial cells recognise carbohydrate groups on cancer cells and allow cancer cells to adhere to endothelial cell at new site in body
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17
Q

Stages of metastasis

A
18
Q

E-cadherin

A
  • Cell linker molcules
  • Links cells together at side
  • Also connects to cytoskeleton
  • Also connects to cytoskeleton within cell
    • Beta catenin links E-cadherin to cytoskeleton
19
Q

What happens to E-cadherin in cancer cells

A

In many cancers

  • E-cadherin expression is reduced, OR
  • E-cadherin is located in the cytoplasm, not the membrane
20
Q

Intergins

A
  • Allow cell to attach to extracellular matrix
  • Linker molecules
  • form heterodimers
  • enable cells to link to extracellular matrix at basal surface (keep cells in position)
  • Recognise different extracellular matrix components such as collegen, laminin, fibronectin, vitronectin
  • Also bind to cytoskeleton
21
Q

Integrins and their role in cancer

A
22
Q

What happens to cells with lost e-cadherin or integrins?

A
  • Loss of E-cadherin or integrins can lead to cultured cells becoming more motile
23
Q

What are the two main types of proteases?

A

Two main types

  • Serine proteases; eg.plasminogen
  • Metalloproteinases (require zinc and calcium) e.g. Collagenase and stromelysin
  • Also secrete protease inhibitors

There is a balance to regulate the composition of the extracellular matrix

24
Q

How are proteases secreted and example?

A

Both types of proteases are secreted in an inactive form as proenzymes

Serine protease precursor plasminogen > active protease plasmin by plasminogen activators

25
Q

How metalloproteinases classified?

A

Metalloproteinases are classified by substrate specificity

26
Q

What happens to proteases in cancer?

A
27
Q

What is angiogenesis?

A

The development of new blood vessels

28
Q

Whats the connection between tumours and angiogenesis?

A
29
Q

What are the benign forms of cancer?

A
  • Fibrodenoma
  • lobular or ductal hyperplasia (can develop into carcinoma in situ)
30
Q

What are the malignant?

A
  • Invasive lobular carcinoma (ILC)
  • Invasive ductal carcinoma (IDC)
31
Q

What are the 5 main molecular subtypes of breast cancer?

A
32
Q

What are some cancer treatments?

A

Traditional

  • surgery
  • chemotherpay
  • radiation therapy

Systemic

  • angiogenesis inhibitors
  • immunotherapy

Targeted

  • horomone therapy
  • monoclonal antibody
33
Q

Chemotherapy

A
  • non-specific intracellular poisons
  • Systemic therapy
  • cytotoxic by means of interfering with cell division (mitosis)

Effects: damage to normal cells that divide rapidly

  • Bone marrow, digestive tract and hair follicles
34
Q

Radiation Therapy and cons with using it

A

Used in conjunction with chemotherapy

  • Ionizing radiation (leads to the formation of free radicals)

Damage DNA

-Has both indirect and direct action

35
Q

What are the characteristics of a tumour microenvironment?

A
  • Decreased blood supply
  • Deficient in oxygen
  • Decreased effectiveness of radiation therapy
36
Q

What is avastin and what does it do?

A

Cancer drug treatment

  • Approved for certtain tumours- glioblastoma, colorectal
  • inhibits growth of blood vessels
  • Adverse events - bleeding, pulmonary embolism
    • Adaptive resistance
37
Q

Name the hormonal and antibody drug selection for breast cancers

A
38
Q

What are benign tumours?

A
  • Remain localised and do not spread
  • Usually do not cause problems unless they grow in a confined space i.e. the brain
39
Q

What is malignant tumours?

A
  • Often have irregular structures, large variable nucleus, little cytoplasm
  • Invade surrounding tissues
40
Q

What are the two hormones involved in human breast?

A
  • Estrogen
  • Progesterone
41
Q

Name two beign breast cancers

A
  • Fibrodenoma
  • Lobular or ductal hyperplasia (can develop into carcinoma in situ)
42
Q

Name malignant breast cancers

A
  • invasive lobular carcinoma (ILC)
  • Invasive ductal carcinoma (IDC)