Neoplasia III *** Flashcards
Give some risk factors of cancer.
- Smoking
- Diet
- Alcohol
- Occupational exposure
What is carcinogenesis and what can cause it?
- Cancer formation
- Normal cells transformed to cancer cells
- Caused by genetic, chemical and microbial factors
Give examples of chemical and viral carcinogens
- Asbestos - mesothelioma
- Benzene - leukaemia
- HPV - cervical carcinoma
- Hep B/C - hepatocellular carcinoma.
Give examples of genes that cause carcinogenesis.
- RB - retinoblastoma
- BRCA1/2 - breast/ovarian cancer
- NF1 - neurofibromatosis
How does asbestos cause cancer?
- When asbestos is broken up, dust forms.
- If dust inhaled, the asbestos fibers will settle in the lungs or in the stomach
- Cause irritation that may lead to mesothelioma.
What occurs normally in cells with DNA damage following carcinogen exposure?
- p53 activation
- Cell cycle arrest at G
- DNA repair mechanisms occur
- If repair fails, apoptosis
What occurs during carcinogenesis in cells with DNA damage following carcinogen exposure?
- p53 not activated due to mutations
- No DNA repair or cell cycle arrest
- Uncontrolled cell proliferation
- Tumour forms
What are the two types of oncogenic viruses?
- RNA viruses - HCV, HTLV-1 (causes lymphoma/T-cell leukaemia)
- DNA viruses - HBV and HPV
How do oncogenic viruses cause a cell to become neoplastic?
- Infection of cell by virus
- Cellular oncogene integrated into genome
- Transduced into host cell
- Forms retroviral DNA which expresses oncogene RNA
How does HPV cause cancer?
- Overexpression of HPV E7 and E6 (oncoproteins)
- E7 inactivates RB gene and CDKIs and activates cell cycle
- E6 degrades p53 gene and upregulates telomerases
Describe proto-oncogenes.
- Used during normal growth and development
- Usually under control
- Have potential to produce neoplasm via excessive expression
Describe oncogenes.
- Activated proto-oncogenes that produce neoplasms
- Promote cell division causing unregulated cell growth
What are the role of tumour suppressor genes?
- Control cell growth e.g by becoming checkpoints in cell cycle
- Loss of genes result in uncontrolled cell growth
What are some methods of conversion of proto-oncogene to oncogene?
- Overexpression/amplification of gene
- Point mutation in gene
- Translocation of gene to another region that will cause overexpression
What are the roles of telomerases in cancer?
- TELOMERES - structures at end of chromosomes that shorten with each cell division until Hayflick limit reached
- Tumours express telomerase activity - causing lengthening of telomeres