Virus-induced Cancers Flashcards
Match the following terms to their definitions:
1) Tumour
2) Benign
3) Malignant
4) Metastasis
5) Transformation
6) Carcinomas
A) tumour that grows progressively and invades other tissues
B) cancers that arise from epithelial cells (most common in humans)
C) a swelling due to abnormal growth of tissue, may be benign or malignant
D) phenotypic changes that a normal cell undergoes as it becomes malignant, normally mediated by DNA alterations
E) growths that do not infiltrate into surrounding tissues
F) movement + colonization by tumour cells to sites distant from the primary site of tumour development
Tumour: a swelling due to abnormal growth of tissue, may be benign or malignant
Benign: growths that do not infiltrate into surrounding tissues
Malignant: tumour that grows progressively and invades other tissues
Metastasis: movement + colonization by tumour cells to sites distant from the primary site of tumour development
Transformation: phenotypic changes that a normal cell undergoes as it becomes malignant, normally mediated by DNA alterations
Carcinomas: cancers that arise from epithelial cells (most common in humans)
(T/F) All human cancers are carcinomas
False! Not all are. Cancers can grow from deeper cells.
1) Cancer is a complex disease that results from growth of successive populations of cells in which _________ and/or ________ __________ of genes and their associated nucleosomes have accumulated.
2) These changes can affect various steps in the _________ pathways that control cell __________, ______, and _______ which can contribute to uncontrolled cell proliferation, and increase in tissue ________, and cancer.
3) One or more of these genetic changes may be _________ or arise as a consequence of endogenous DNA ______ and exposure to environmental entities.
1) mutations; epigenetic modifications
2) regulatory; communication; growth; division; disorganization
3) inherited; damage
Which one of the statements is true regarding cancer cells?
1) Cancer cells do not bypass normal controls that regulate growth & proliferation
2) A benign glandular tumor remains inside the basal lamina that marks the boundary of the normal structure
3) A malignant glandular tumor never develops from a benign tumor cell, but they can destroy the integrity of the tissue
4) Growth of tumors usually occurs over a span of days
2!
For 1: Cancer cells bypass normal controls that regulate growth & proliferation
For 3: A malignant glandular tumor MAY develop from a benign tumor cell, AND can destroy the integrity of the tissue
For 4: Growth of tumors can take weeks and decades
(T/F) Cancer development is a multi-step process whereby the accumulation of a set of genetic changes leads to the tumor cell phenotype. These changes always occur in a defined order.
False!
These changes can occur in a defined order or ACCUMULATE RANDOMLY. As a result, there are multiple routes by which a cell can reach a malignant state.
What are the three routes by which a cell can reach a malignant state (normal cell -> precancer cell -> cancer cell)?
Which one is the most common?
1) Ordered sequence of genetic changes
2) Random accumulation of genetic changes
3) Combination of ordered and random genetic changes (single genetic change and then random and multiple genetic changes)
Number 3 is the most common.
(T/F) The specific nature of early events in the pathway by which a cell can reach a malignant cell likely predisposes cells to suffer further mutations.
True!
An example of combination of ordered and random genetic changes is colorectal cancer. Briefly describe the typical sequence of genetic alterations of colorectal cancer.
There is a driving mutation (loss of Apc) going from a normal cell to precancer cell.
Then, there are series of events such as ACTIVATION of ONCOGENES and LOSS of or INACTIVATION of TUMOR SUPPRESSORS leading to a cancer cell.
There is an acquisition of increased genetic and epigenetic instability during this process.
Match the following terms with their definitions:
1) Tumor suppressor genes
2) Proto-oncogene
3) Oncogene
A) mutated, overactive /overexpressed, altered forms of proto-oncogenes whose protein products has potential to contribute to tumor development.
B) genes that encode proteins that LIMIT cell proliferation. these genes normally prevent the formation of tumors. these are lost or inactivated in cancers.
C) genes that encode proteins that normally processes such as cell growth, division, differentiation, survival. Mutated form/altered expression of a proto-oncogene may be referred to as an oncogene.
Tumor suppressor genes: genes that encode proteins that LIMIT cell proliferation. these genes normally prevent the formation of tumors. these are lost or inactivated in cancers.
Proto-oncogene: genes that encode proteins that normally processes such as cell growth, division, differentiation, survival. Mutated form/altered expression of a proto-oncogene may be referred to as an oncogene.
Oncogene: mutated, overactive /overexpressed, altered forms of proto-oncogenes whose protein products has potential to contribute to tumor development.
(T/F) Tumor suppressors function in a dominant manner whereas oncogenes function in a recessive manner.
False!
Oncogenes function in a DOMINANT manner, meaning that a gain of function mutation in ONE gene copy can contribute to tumor development.
Mutations in tumor suppressor genes function in a RECESSIVE manner, meaning that BOTH gene copies must be affected to drive tumorigenesis.
What are the four events that can convert a proto-oncogene to an oncogene? What do they lead to?
1) Deletion or point mutation in coding sequence (makes HYPERACTIVE PROTEIN in normal amount)
2) Regulatory mutation (normal protein greatly overproduced)
3) Gene amplification (normal protein greatly overproduced)
4) Chromosome rearrangement (nearby regulatory DNA sequence causes normal protein greatly overproduced or fusion to actively transcribed gene produces hyperactive fusion protein)
Briefly answer the following questions regarding p53:
1) What are the roles of p53?
2) What happens to p53 in unstressed cells?
3) How is p53 activated?
1) p53 is a tumor suppressor. It leads to cell cycle arrest, DNA repair, block of angiogenesis, apoptosis
2) In unstressed cells, p53 protein levels are very low because it is targeted for proteasomal degradation by the E3 ubiquitin ligase MDM2.
3) p53 is activated in response to many stress stimuli, including activation of oncogenes and DNA damage. Upon activation, p53 directly regulates the transcription of ~500 genes and thereby controls diverse cellular processes.
(T/F) The gene that encodes p53 is mutated in approximately 50% of all cancers, highlighting its importance as a tumor suppressor.
True
Briefly answer the following questions regarding Rb:
1) What is Retinoblastoma (Rb)?
2) What happens when mitogens (chemicals/signaling molecules like GFs) are present?
3) What happens when mitogens (chemicals/signaling molecules like GFs) are absent?
1) Rb is a TUMOR SUPPRESSOR PROTEIN whose function is controlled by exogenous factors (mitogens) that will induce a signalling cascade that will lead to the inactivation by phosphorylation of Rb.
2) When mitogens are present, they bind to cell surface receptors that initiate signal transduction cascades that induce expression of transcription regulatory proteins. This allows the activation of G1-Cdks which PHOSPHORYLATE and INHIBIT Rb, liberating transcription factor E2f, allowing expression of cell cycle genes and PROGRESSION THROUGH S PHASE.
3) In the absence of mitogens, Rb protein binds and inhibits the E2f transcription factor, resulting in NO EXPRESSION of S phase genes and no cell cycle progression.
What are some examples of hallmark features of cancer?
1) sustaining proliferative signalling (uncontrolled cell proliferation)
2) evading growth suppressors
3) resisting cell death
4) enabling replicative immortality
5) inducing angiogenesis
6) activation invasion and metastasis
7) reprogramming energy metabolism
8) evading immune destruction
