Chapter 13 Flashcards
How does extrinsic inflammation play a role in the formation of cancer?
Intrinsic inflammation is inflammation happening inside the body, caused by one’s own immune system. Intrinsic inflammation can create a suitable microenvironment for tumors to grow and develop.
What are a few examples of viruses (and more) that can cause cancer?
- Epstein-Barr virus (EBV)
- Human Papillomavirus (HPV)
- Human T-cell lymphotropic virus type 1 (HTLV-1)
- Hepatitis B virus (HBV)
- Kaposi’s sarcoma-associated herpesvirus (KSHV)
- Helicobacter pylori (gut bacteria)
What types of cancer does Epstein-Barr cause?
Several types of lymphoma an nasopharyngeal cancer.
What oncoprotein in EBV is associated with human cancer and what does it do?
EBV encodes a protein called LMP1 in human DNA. It activates genes that promote cell proliferation (EGFR) and genes that inhibit apoptosis (Bcl-2)
What kind of cancer does HPV cause?
It is the most common sexually-transmitted virus and it causes cervical cancer. Virtually 100% of cervical cancers are caused by HPV.
Which HPV proteins play a major role in carcinogenesis?
Proteins E6 and E7.
E7 can bind to and activates the degradation of RB, which inhibits the sequestration of E2F. Active E2F leads to cell proliferation.
E6 binds to ubiquitin ligases and forms a complex. The E6-ligase complex target and degrade p53 proteins.
What kind of cancer does HTLV-1 cause?
Almost all cases of T-cell lymphoma are found to involve HTLV-1. This is also the only retrovirus found to cause cancer in humans.
What is the mechanism of HTLV-1?
The virus uses reverse transcriptase to put its RNA coding sequences into human DNA. The main player protein TAX has an array of effects, including cell proliferation, inhibition of DNA repair, activation of cdks.
Name an indirect mechanism of HBV in the causation of liver cancer?
An indirect mechanism involves the causation of inflammation at the site of infection, which can initiate tumor growth.
What are the two direct mechanisms of HBV in causing cancer?
- Integration of viral DNA in the genome and activation of human telomerase reverse transcriptase (hTERT)
- The expression of HBV X protein, which has a role in activating the RAS pathway and inactivating p53
What cancer does KSHV cause?
Kaposi Sarcoma and primary effusion lymphoma.
What do cells infected with KSHV need in order to grow?
Cells infected need cytokines and growth factors to grow. These external signals are gained by forcing neighboring cells to produce the cytokines and growth factors so the cells can develop.
What are the steps to carcinogenesis initiated by H. Pylori?
- Infection
- Chronic superficial gastritis
- Atrophic gastritis
- Intestinal dysplasia
- Gastric carcinoma
what kind of cancer does H. Pylori cause?
Gastric cancer.
How can Gastric Atrophy lead to inflammation?
Gastric atrophy is characterized by the loss of gastric glandular cells, which in turn produce less acid. A less hostile environment in the stomach leads to bacteria being able to colonize it and lead to an inflammation
What is the protein that plays a main role in cancer induced by H. Pylori?
Protein Cytotixoc-Associated Antigen A (Cag A)
What is the mechanism of action of Cag A?
Cag A enters the cell. Cag A is then phosphorylated by a tyrosine kinase and binds to SHP-2. SHP-2 is then activated
What is the relation between E-cadherin and Cag A?
Cag A activates DNA methyltransferases, leading to hypermethylation. The E-cadherin promoter gets silenced by methylation
Which important oncogenes can induce inflammatory cytokines?
RAS and Myc.
The activation of transcription factors do inflammatory responses lead to?
Transcription factors STAT and NF-kB
What is the function of STAT?
Promotes cell growth by inducting Cyc D, Cyc B, and Myc. It also increases survival by inducting anti-apoptotic proteins.
What does NF-kB do?
NF-kB is a transcription factor that keeps pro-inflammatory genes under control. NF-kB can be induced by carcinogens and start an inflammatory reaction
How does inflammation lead to cancer?
During inflammation, cells produce ROS and NOS, which can cause DNA damage to the infected cells as well as healthy cells.
How can Tumor-Associated Macrophages induce tumor growth?
TAMs can release TNF-a around the tumor tissue, which can work as a tumor promoter if unregulated.
What are some effects downstream of NF-kB?
- Inhibition of Apoptosis
- Inflammation
- Metastasis
- Angiogenesis
How does the transcription of NF-kB get activated during carcinogenesis?
- Continuous exposure to inflammatory agents
2. Aberrant expression of the gene
