Biochemistry 2280A Lecture Notes - Lecture 18: Xeroderma Pigmentosum, Basal Lamina, Cervical Cancer
5 May 2018
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Cancer
- Leading cause of death in North America
- Characterized by genetic and biochemical defects
- Characterized by rapid proliferation of an abnormal
cell derived from one of the orgais’s o ell that
has undergone inheritable change and lost control of
cell growth and differentiation.
Tumour Types
1. Benign
- Do not spread from original site
2. Malignant
- Do spread from original site (metastasize) and
invade surrounding tissues
Cancer is a Genetic Disease
Some types can be inherited:
- retinoblastoma (eye cancer)
- xeroderma pigmentosa (skin cancer)
- breast, prostrate, ovarian and intestinal cancers
Causes of Cancer
1. DNA-damaging agents
- Radiation (UV light (causes thymine dimers), X-ray light)
- Chemical Mutagens (benzene, formaldehyde)
2. Chemicals that Cause Cell Division
- Tumour Promoters (do’t diretly ause DNA daage, ut stiulate
cell proliferation (division) enhanced cell # = increase in probability
that a mutant cell will appear and turn into a caner cell)
3. Viruses Use vaccines to limit acquiring viruses
- Hepatitis (Hep. B liver cancer), HPV (cervical cancer and others;
no current cure), HIC (Kaposi sarcoma, Non-Hodgki’s lyphoa
*Smoking is the most preventable cause of cancer (smoking causes 30% of
all cancers, and 90% of lung cancer). Smoking causes DNA damage (ex.
polonium-210 radioactively decays, leading to DNA breaks)
Tumour Progression
- Cancer risk increase w/age b/c multiple mutations
accumulate over time.
- A single mutation is’t suffiiet to ause aer,
tumour progression involves multiple (10+) rounds of
specific mutations that accumulate and cause the
disease (mutations can be in DNA repair machinery or
other mutations that allow cells to grow faster or in
abnormal places)
*Most cancers derive from a
single abnormal cell
- First mutation may allow the
cell to grow more quickly
- Second mutation may allow
the cells to grow in the absence
of the basal lamina
- Third mutation may allow the
cells to penetrate the basal
lamina.
- After 10 mutations dangerous
cell proliferation occurs, and
cancer ensues.
Properties of Cancer Cells
1) They do’t hae the sae opleet of DNA as normal cells
(they have mutations)
2) They divide in the absence of growth factors
3) They are immortal - they do’t respod to sigals that trigger
cell death (ex. they can divide even when in contact w/other cells
and they express telomerase)
4) Have lost control of the cell cycle (ignore cell checkpoints
results in chromosome abnormalities)
5) Are genetically unstable (more point mutations, copy #
variations, major chromosome abnormalities)
6) Multiply in abnormal places that are atypical for the
originating cell type (via. metastasis)
Cancer Causing Genes
1. Oncogenes
- mutant form of a normal gene whose presence
causes cancer (dominant gain/altered function)
3 types of single mutation events
1) Point Mutation in the proto-oncogene that results
in hyperactive protein made in normal amounts
2) Gene Amplification of proto-oncogene resulting in
normal protein being greatly overexpressed.
3) Chromosomal Rearrangement causing proto-
oncogene to be beside a regulatory DNA sequence
that causes overexpression of the proto-oncogene or
one that causes proto-oncogene to fuse with another
gene, causing hyperactive protein.
2. Tumor Suppressor
- gee’s asee auses aer reessie loss of fn)
Proto-oncogene
Function of Cancer Causing Genes
- most oncogenes + tumour suppressor genes
code for proteins that regulate cell division or
cell differentiation
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
Cancer risk increase w/age b/c multiple mutations accumulate over time. Leading cause of death in north america. Characterized by rapid proliferation of an abnormal cell derived from one of the orga(cid:374)is(cid:373)"s o(cid:449)(cid:374) (cid:272)ell that has undergone inheritable change and lost control of cell growth and differentiation. Mutant form of a normal gene whose presence causes cancer (dominant gain/altered function) Do not spread from original site: malignant. Do spread from original site (metastasize) and invade surrounding tissues. *most cancers derive from a single abnormal cell. Ge(cid:374)e"s a(cid:271)se(cid:374)(cid:272)e (cid:272)auses (cid:272)a(cid:374)(cid:272)er (cid:894)re(cid:272)essi(cid:448)e loss of fn) First mutation may allow the cell to grow more quickly. Second mutation may allow the cells to grow in the absence of the basal lamina. Third mutation may allow the cells to penetrate the basal lamina. After 10 mutations dangerous cell proliferation occurs, and cancer ensues. Radiation (uv light (causes thymine dimers), x-ray light) Chemical mutagens (benzene, formaldehyde: chemicals that cause cell division.
