Lecture 28: Cancer 1 Flashcards
Which type of cancer is the most deadly?
Lung
If the indecency of breast cancer is the same as that of lung cancer, why is the survival rate different?
You can remove a tumor from the breast, but you typically cannot remove from the lung
What are the 2 most common causes of death?
Cancer and heart attacks
What age group is primarily affected by cancer?
45-65
Deaths in those <40 are from accidents, >65 is heart failure
Why is cancer considered a disease of aging?
We accumulate mutations with age that are necessary for cancer to develop
________ is a disease in which an individual mutant clone of cells begin by prospering at the expense of its neighbor cells. Descendents of these clones can destroy the whole cell society in your body
Cancer
What 2 types of signals are cancer cells able to ignore in order to become self-sustaining?
Anti-growth signals
Apoptotic signals
What type of signals to cancer cells release themselves to become self-sustaining?
Autocrine growth factor signals
What controls cell growth and what produces these?
Growth factors - produced by other cells to stimulate target cells to divide (for healing or growth)
Cells do not divide unless told to do so!
What is one important biological distinction between cancer cells and normal cells in terms of growth factor?
Cancer cells require little growth factors
Normal cells have strong requirement!
Thus, cancer cells become independent of stimulation that is normally required by cells to proliferate (decontrolled proliferation)
What are the 2 heritable properties of cancer cells?
- Reproduce despite normal restraints on cell division and growth
- Invade areas normally reserved for other cells
How does cancer eventually kill?
As a tumor grows and spreads, it squeezes or destroys blood vessels and nerves until an organ can no longer perform its functions – death results
An abnormal cell that grows (increases in mass) and proliferates out of control will give rise to a tumor or ___________ ___________
Neoplastic growth
Differentiate between benign and malignant tumors
Benign tumors are neoplastic cells that do not become invasive, and the growth may be surgically removed as a cure
Malignant tumors have the ability to invade surrounding tissues
True or false: a benign tumor is considered cancerous
False
What class of cancer is from epithelial cells?
Carcinoma
What class of cancer is from connective tissue and muscle tissue?
Sarcoma
What class of cancer is from white blood cells and their precursors?
Leukemias and Lymphomas
What class of cancer is most common?
Carcinomas
Benign tumors are also known as ____________, which are benign epithelial tumors with glandular organization
Adenoma
Malignant tumors are also known as ____________
Adenocarcinomas
Cancers have names reflecting tissue origin.
What type of cancer originates in a keratinocyte stem cell in skin?
Basal cell carcinoma
Cancers have names reflecting tissue origin.
What type of cancer originates in pigment cells in skin?
Melanoma
Differentiate between basal cell carcinoma and melanoma in terms of metastasis
Basal-cell carcinoma rarely metastasizes while malignant melanoma metastasizes widely
What term describes the invasiveness of cancer - meaning that it can break loose, enter into blood or lymph, travel to new areas, and form secondary tumors
Metastasis
Tumor development involves multiple mutational events which confer a proliferative advantage. All tumors come from a __________ ___________
Single ancestor
Describe tumor progression in 3 basic steps
- Benign growth
- Invasive cancer
- Metastasis
Tumor development, like that which occurs in colon cancer, begins how?
With a mutation in APC gene, which is a tumor suppressor -> leads to formation of polyps
After the formation of polyps in colon cancer, which remains a benign tumor that does not move away from its point of origin, how does malignant cancer develop?
Mutation in Ras - which becomes a cancer gene
Additional loss of other tumor suppressor p53, results in invasion into epithelial cells and tumor can now move out into bloodstream and invade other tissues
What is the primary evidence that cancer comes from a single heritable cell?
A translocation between Chr 9 + 22 on the Philadelphia chromosome results in chronic myelogenous leukemia
What type of mutations do cancer cells contain?
Somatic
Carcinogenesis is linked to what?
Mutagenesis - mutant change in DNA
What are the 2 primary types of carcinogens?
Chemical
Radiation (x-rays, UV)
What are the 3 biological mechanisms that prevent our relatively high mutation rate from causing cancer at an early age?
DNA repair mechanisms
Cell cycle controls
Apoptosis
The cervix is _______ epithelia. When cancer develops, cell proliferation begins in ______ epithelia, resulting in low->high grade intraepithelial neoplasia
Stratified; basal
When does cervical cancer become malignant?
When cells move through the basal lamina, invade surrounding tissues, and enter bloodstream
How is obesity related to the increased incidence of cancer?
More cells –> more chances for mutation
True or false: Metastases cannot be eradicated by surgery OR radiation treatment
True
______________ is the formation of new blood vessels basically from scratch
Neovascularization
______________ is when new blood vessels sprout from pre-existing blood vessels
Angiogenesis
Why are processes like neovascularization and angiogenesis important to cancer cells?
Tumors must get oxygen and nutrients like normal cells, so they release factors to induce new blood vessel formation
[this makes them a good target for cancer therapy -Folkman]
Stromal cells consist of what two cell types?
Fibroblasts
WBCs
Cancer cells get help from stromal cells
What type of diet accounts for 37% of bowel, pancreas, prostate, and breast cancers?
High fat/low fiber
What accounts for 24% of lung, kidney, and bladder cancers?
Tobacco use
What test is used to determine if a substance is mutagenic? What amino acid is used in this test?
Ames test; requires bacteria needing histidine
What 2 viruses did we discuss that can contribute to human cancer?
HIV can cause Kaposi’s sarcoma
Helicobacter pylori can cause stomach cancers
What is the term referring to genes whose alteration frequently results in cancer?
Cancer critical genes
What are the 2 broad types of mutations of genes that regulate cell proliferation - leading to cancer?
Overactivity mutations
Underactivity mutations
What type of genes are involved in overactivity mutations?
What is the result?
Dominant or Recessive?
Oncogenes
Gain of function
Dominant
What type of genes are involved in underactivity mutations?
What is the result?
Dominant or Recessive?
Tumor suppressor genes
Loss of function
Recessive
What type of mutation involves genes that inhibit growth, and the first mutation has no effect but second mutation causes problems?
Underactivity mutations - loss of function - tumor suppressor genes - recessive
What type of mutations involve a single mutation event and activation of a gene causing proliferation?
Overactivity - gain of function - oncogenes - dominant
What group of genes is considered a subset of tumor suppressor genes?
DNA maintenance genes
What are the 2 types of DNA maintenance genes?
DNA repair genes and checkpoint genes
In 1911, Peyton Rous discovered a virus called RSV that could cause cancer in chickens. RSV is a retrovirus, what does this mean?
It contains an RNA genome which must be reverse transcribed in a host to be incorporated into host genome - resulting in transformed cells
What are “transformed cells”?
Small colonies of proliferating cells caused by oncogene
What does transformation activity of RSV depend on?
V-src oncogenes
Viral oncogenes have closely related gene counterparts in normal cells called _______, which are involved in cell growth and proliferation
c-src
What happens when a virus hijacks c-src?
It makes a mutation so that c-src is activated like crazy
What are the 2 ways that retroviruses hijack protooncogenes?
Over-expression (from strong viral promotor)
Mutate proto-oncogen into oncogene
What is considered the first human oncogene?
Ras
Ras is the monomeric GTPase for signal transduction, so what is characteristic of a Ras oncogene?
They cannot shut off by hydrolyze GTP to GDP (like in cholera infection)
Results in intracellular signal transducer molecule overproduction (Ras)
What are the 4 types of oncogene activation?
- Deletion or point mutation in coding sequence
- Regulatory mutation
- Gene amplification
- Chromosome rearrangement
In the activation of oncogenes, what is the restful of a deletion or point mutation in the coding sequence?
Hyperactive protein made in normal amounts
In the activation of oncogenes, what is the restful of a regulatory mutation?
Normal protein greatly overproduced (promoter mutation)
In the activation of oncogenes, what is the restful of a gene amplification?
Several copies are made instead of 1 copy - normal protein is overproduced
In the activation of oncogenes, what is the restful of a chromosomal rearrangement?
Brings new regulatory sequence that causes overproduction OR creates overactive fusion protein
How does cancer alter ligand/receptor relationships in cells?
Cancer cells produce their own ligands for autocrine signaling
Alter RTKs so they don’t even need a ligand
How do transcription factors relate to cancer?
These proteins constantly induce transcription, activating gene expression, including those important for cell cycle progression (over production can lead to oncogene)
How does Bcl2 relate to cancer?
Bcl2 inhibits apoptosis despite DNA damage
What type of mutation is the Bcl2 oncogene?
Rearrangement mutation
In cancer cells, Bcl2 locus on Chr 18 undergoes reciprocal translocation with part of Chr 14 gene. This places Bcl2 under control of enhancer that is very active in B cells and results in the expression of Bcl2 instead of Ab. What type of cancer is this?
B cell lymphoma
