Cancer vs genetic disease. Similarities and differences
- Both due to mutation
- Cancer is from multiple mutations in somatic cells
- Genetic disease if from single mutation in germ cells
_____ are the stages of cancer and their characteristics.
- Tumor: mass of cells with a porpensity to grow without obeying the rules of growth regulation
- Benign: slow- growing tumors
- Malignant: Invasive and lead to morbity by taking up space or secreting too much of a biological compound (dedifferentiated)
_____ are the 6 changes in a cell that cause cancer.
- Self-sufficiency in growth signals
- Insensitivity to antigrowth signals
- Evasion of apoptosis
- Limitless replicatice potential
- Tissue invaseion and metastasis
- Sustained angiogenesis
_____ are the 5 general characteristics of Tumor cells.
- Abnormal and unstable numbers of chromosomes
- Benign tumors may progress to malignancy with time
- High nucleus to cytoplasmic ratio
- High number of mitotic figures
- Presence of invading cells in normal tissue
_____ are the 3 classifications of malignant tumors.
- Simple: Tumor originates from a single type of germ layer (mesenchymal or epithelial)
- Mixed: Tumor originates from a single germ layer but has multiple tissue origins
- Compound: Tumor originates from more than one germ layer and more than one tissue
____ are the 8 characteristics of malignant tumors.
CAN - I - A
- Growth in suboptimal Conditions
- Lost Ability to regulate cell cylce
- eNnzymes that destroy connective tissue
____ are the first steps in metastasis.
Cancer cells leave the tumor and attack the basement membrane with invadopodia and by secreting plasminogen which helps breakd down membrane. Cells then travel along ECM by following EGF secreted by macrophages until they reach a blood vessel.
Cancer is a multistep process. In colorectal carcinoma __#__ of mutations occur on __4 proteins__. These mutations result in ____ for the proteins which has ____ effect on cacer progression.
- ACP - 2 mutations = loss
- K-ras - 1 mutation = activation
- DCC - 2 mutations = loss
- p53 - 2 mutations = loss
ACP is a ____ gene and mutation in this gene causes ____.
- Tumor supressor
- Polyp formation = benign/precancerous tumor
K-ras is a _____ and causes _____
Increased cell proliferation and polyp growth = class II adenoma.
DCC is a _____ protein involved in colorectal cancer and signifies the progression to ____ adenoma.
VHL is a ____ which involves ____.
Rare inherited genetic disease which involves abnormal growth of tumors in parts of boy particularly rich in blood supply.
A loss of pVHL, which is ____, causes increased levels of ____ and ____.
- Tumor suppressor
- HIF (hypoxia inducible factor)
- VEGF + EPO which are angiogenic factors
____ are the four main angiogenesis genes.
Simply - describe stem cells in their niche.
SC divides asymetrically to produce new SC that stay in the niche and proliferative cells that move out of the niche and become progenitor cells. The proliferative capacity becomes less and less with each cell division and eventually the cells become completely differentiated.
____ are the 4 ways tumors may arise from normal stem cells by circumventing "Niche-dependent Restrictions"
- Expansion of stem cell niche - niche gets bigger allowing cancer cells to increase in population - kept happy/safe in niche
- Alterations in cancer stem cells that allows them to adapt to a new niche
- Genetic or epigenetic alteations in caner stem cells - cell becomes independant of niche and self-renewal is autonomous
- Mutations arise - progenitors gain ability of self-renewal
Overview of why niche is important in stem cell and cancer formation.
SC niche provides growth factors and nutrients for stem cells to proliferate and differentiate. If cell becomes cancerous it can exploit these signals until it is able to do so on its own.
Describe the hematapoietic tree.
- Hematapoietic pluripotent cell gives rise to :
- Myeloid and Lymphoid stem cells
- Myeloid stem cells become blood cells
- Lymphoid stem cells become immune cells
_____ is the physical property that makes a chemical carsinogenic because ____.
REactive electrophiles or chemicals are metabolically converted to reactive electrophiles because DNA is nucleophilic
Ethyl methansulfate (EMS) is a ____ and causes ____.
Direct carcinogen (carcinogen in original form) and causes Guanine alkylation which converts a G:C to A:T
Describe process of G1 arrest in response to DNA damage.
- DNA damage activates ATM
- ATM activates Chk2 and p53
- Chk2 activates Cdc25A and p53
- Cdc25A - degraded by proteosome so CDK2 is not activated
- Active p53 activates trx which leads to apoptosis, sustained DNA repair, G1 and G2 arrest
Name the 7 types of proteins that participate in controlling cell growth and proliferation + 2 categories these fit into.
- Oncogenes: Extracellular signalling molecules, Signal receptors, Signal transduction proteins, transcription factors
- Tumor suppressors: DNA repair proteins, Cell cycle control proteins, and apoptotic proteins
How does Rb work? What regulates Rb? What are the common problems that lead to cancer? What virus exploits this pathway?
- Tumor suppressor that binds and prevents E2F trx
- Cyclin D - CDK4 which is regulated by complex with p16
- overproduction of cyclin D and loss of negative regulators p16 and p53
- HPV - E7 inactivates Rb = E2F activation
Name 4 viruses associated with human cancers.
HPV, Hep B, Epstein Barr, HTLV