Export your learner materials as an interactive game, a webpage, or FAQ style cheatsheet.
Unsaved Work Found!
It looks like you have unsaved work from a previous session. Would you like to restore it?
Total Categories: 6
Metastasis is defined as the process by which tumor cells migrate from the primary cancer site to a distant location, where they form secondary tumors.
Answer: True
Metastasis is defined as the process by which tumor cells migrate from the primary cancer site to a distant location, where they form secondary tumors. This is a critical hallmark of advanced cancer.
Human breast cancer commonly metastasizes to organs such as the kidneys, spleen, and pancreas.
Answer: False
Human breast cancer commonly metastasizes to distant organs such as the brain, lungs, bones, and liver, not typically to the kidneys, spleen, or pancreas.
The classical theory of metastasis, developed in the early 1970s, proposed that metastasis arises from genetically identical subpopulations within primary tumors.
Answer: False
The classical theory of metastasis, developed in the early 1970s, proposed that metastasis arises from genetically determined subpopulations within primary tumors, not necessarily genetically identical ones. This implies distinct evolutionary pathways within the tumor.
Tumor heterogeneity implies that genetic variance between metastatic foci is significant for only particular genetic loci and within specific cell populations.
Answer: True
Tumor heterogeneity implies that genetic variance between metastatic foci is significant for only particular genetic loci and within specific cell populations. This means that some loci might diverge in only one cell subpopulation, contributing to the overall genetic diversity observed.
Genes that drive growth at the primary tumor site are distinct from those that determine the dissemination and colonization of cancer cells at distant sites.
Answer: False
Genes driving primary tumor growth are often not distinct from those that determine the dissemination and colonization of cancer cells at distant sites; there can be significant overlap and shared regulatory mechanisms.
Breast cancer is considered genetically and clinically heterogeneous because it originates from diverse normal breast tissue.
Answer: True
Breast cancer is considered heterogeneous because it reflects the diversity and variations present in the normal breast tissue from which it originates. This heterogeneity is observed both genetically and clinically.
The metastatic potential of subpopulations within mouse mammary cells is now considered to be a relatively late event, occurring only after the primary tumor has fully formed.
Answer: False
The metastatic potential of subpopulations within mouse mammary cells is now considered to be a relatively early event, with dissemination occurring concurrently with pre-invasive or micro-invasive lesions.
The genetic profiles of primary breast carcinomas and their metastases show a significant extent of clonal relatedness between the lesions, indicating a shared origin.
Answer: True
The genetic profiles of primary breast carcinomas and their metastases show a significant extent of clonal relatedness between the lesions, indicating a shared origin.
Breast cancer phenotypes express genes that are indispensable for the metastatic process, with diversity mediated by the activation of genes that couple to organ-specific growth.
Answer: True
Breast cancer phenotypes periodically express genes that are indispensable for the metastatic process, with diversity in metastatic behavior mediated by the activation of genes that facilitate organ-specific growth.
The growth of lesions at ectopic sites is solely dependent on the genetic makeup of the metastatic cells themselves.
Answer: False
The growth of lesions at ectopic sites depends on complex interactions between the metastatic cells and the host's homeostatic mechanisms. Lethal protein-protein interactions at the metastatic site can aid the survival of adapted cells.
What is the primary definition of metastasis in the context of breast cancer research?
Answer: The migration of tumor cells from the primary site to a distant location, forming secondary tumors.
Metastasis is defined as the process by which tumor cells migrate from the primary cancer site to a distant location, where they form secondary tumors. This is a critical hallmark of advanced cancer.
Which of the following organs is commonly cited as a site for human breast cancer metastasis?
Answer: Lungs
Human breast cancer commonly metastasizes to distant organs including the brain, lungs, bones, and liver.
According to the classical theory developed in the early 1970s, what was proposed as the origin of metastasis?
Answer: Metastasis arises from genetically determined subpopulations within primary tumors.
The classical theory of metastasis, formulated in the early 1970s, posited that metastasis originates from genetically distinct subpopulations within primary tumors.
What does tumor heterogeneity imply regarding genetic variance in metastatic tumors?
Answer: Genetic variance between metastatic foci is significant for only particular genetic loci and within specific cell populations.
Tumor heterogeneity indicates that genetic variance among metastatic foci is pronounced at specific genetic loci and within particular cell populations, suggesting that divergence may occur in isolated subpopulations, thereby contributing to overall genetic diversity.
Which statement best describes the relationship between genes driving primary tumor growth and dissemination/colonization?
Answer: Genes driving primary growth can also determine dissemination and colonization at distant sites.
Genes responsible for primary tumor growth can also govern the dissemination and subsequent colonization of cancer cells at distant, ectopic sites.
Why is breast cancer considered a genetically and clinically heterogeneous disease?
Answer: It reflects the diversity and variations present in the normal breast tissue of origin.
Breast cancer is deemed heterogeneous due to its reflection of the inherent diversity and variations found within the normal breast tissue of origin, manifesting in both genetic and clinical characteristics.
When is the metastatic potential of subpopulations within mouse mammary cells considered to occur?
Answer: As a relatively early event, concurrent with pre-invasive or micro-invasive lesions.
The metastatic potential of subpopulations within mouse mammary cells is now understood to manifest as a relatively early event, with dissemination occurring concurrently with pre-invasive or micro-invasive lesions.
What do the genetic profiles of primary breast carcinomas and their metastases reveal?
Answer: A significant extent of clonal relatedness between the lesions, indicating a shared origin.
Genetic profiles of primary breast carcinomas and their metastases consistently reveal a significant degree of clonal relatedness, substantiating a shared cellular origin.
Clarence C. Little developed the first inbred mouse strain, named the C57BL, in 1909.
Answer: False
Clarence C. Little developed the first inbred mouse strain in 1909, which was named the DBA (Dilute, brown non-Agouti) mouse. The C57BL strain was developed later.
In 1915, N.M. Haldane identified the first genetic linkage in mice between Albino mice and pink eye dilution on chromosome seven.
Answer: True
In 1915, N.M. Haldane identified the first genetic linkage in mice, specifically between the Albino gene and pink eye dilution, located on chromosome seven.
The C57BL mouse strain was the first to have its genome sequenced.
Answer: True
The C57BL mouse strain emerged as one of the most extensively utilized in genetics and was the inaugural strain to undergo genome sequencing.
In 1982, Palmiter and Brinster generated the first transgenic mice by implanting a foreign gene into a fertilized egg, engineering them to express recessive oncogenes.
Answer: False
In 1982, Palmiter and Brinster achieved a groundbreaking feat by generating the first transgenic mice through the implantation of a foreign gene into a fertilized egg, thereby engineering them to express dominant oncogenes, which is crucial for observing phenotypic effects.
Who is credited with developing the first inbred mouse strain in 1909?
Answer: Clarence C. Little
Clarence C. Little developed the first inbred mouse strain in 1909, designated as the DBA (Dilute, brown non-Agouti) mouse.
What significant genetic discovery was made by N.M. Haldane in 1915 regarding mice?
Answer: The first genetic linkage in mice between Albino mice and pink eye dilution on chromosome seven.
In 1915, N.M. Haldane identified the first genetic linkage in mice, specifically between the Albino gene and pink eye dilution, located on chromosome seven.
Which mouse strain was the first to have its genome sequenced and became widely used in genetics?
Answer: C57BL
The C57BL mouse strain emerged as one of the most extensively utilized in genetics and was the inaugural strain to undergo genome sequencing.
What groundbreaking achievement in genetic engineering of mice occurred in 1982?
Answer: The generation of the first transgenic mice by implanting a foreign gene.
In 1982, Palmiter and Brinster achieved a groundbreaking feat by generating the first transgenic mice through the implantation of a foreign gene into a fertilized egg, thereby engineering them to express dominant oncogenes.
The 4T1 cell line is an example of a metastatic mouse mammary carcinoma cell line used in research.
Answer: True
Exemplary metastatic mouse mammary carcinoma cell lines utilized for identifying genes and pathways involved in metastasis include 4T1 and TS/A, which exhibit metastatic behavior in syngeneic immunocompetent mice.
The Mouse Mammary Tumor Virus (MMTV) acts as a promoter that can induce breast tumors when activated, facilitating steroid-hormone-inducible transcription via its long terminal repeat (LTR).
Answer: True
The Mouse Mammary Tumor Virus (MMTV) functions as a promoter, particularly its Long Terminal Repeat (LTR), which can induce breast tumors upon activation, often via steroid-hormone-inducible transcription. Viral genome integration into critical cellular regulatory genes can also lead to tumorigenesis.
The MMTV-PyMT model is the most commonly used model for studying mammary tumor progression and metastasis.
Answer: True
The MMTV-PyMT model is significant as it is widely recognized as the most prevalent model for investigating the complex processes of mammary tumor progression and metastasis due to its rapid development of highly metastatic tumors.
The MMTV-HER2/neu model uses the MMTV-LTR to promote the expression of the receptor tyrosine-protein kinase ErbB3, which is amplified in human breast cancers.
Answer: False
The MMTV-HER2/neu model uses the MMTV-LTR to promote the expression of the receptor tyrosine-protein kinase ErbB2 (HER2), not ErbB3. ErbB2 amplification is a known driver in human breast cancers.
The Whey acidic protein (WAP) promoter is rarely used in generating mouse mammary cancer models compared to MMTV.
Answer: False
In addition to MMTV, the Whey acidic protein (WAP) promoter is frequently employed for generating mouse mammary cancer models.
Acute ablation of TGF-β signaling in MMTV-PyMT mammary tumor cells led to a significant decrease in lung metastasis.
Answer: False
Acute ablation of TGF-β signaling in MMTV-PyMT mammary tumor cells resulted in a significant increase in lung metastasis, indicating TGF-β1's role in regulating metastatic dissemination.
The MMTV-HER2/neu model was modified by fusing the mouse neu gene with a rat neu gene to improve its accuracy in representing HER2 gene amplification.
Answer: True
To more accurately model HER2 gene amplification, researchers fused the mouse neu gene with its rat counterpart. This modification improved model fidelity compared to the non-fused mouse version, which exhibited mammary gland reversion.
The MMTV-PyMT model uses the MMTV-LTR to drive the expression of the polyomavirus middle T-antigen, leading to rapid development of highly metastatic tumors.
Answer: True
The MMTV-PyMT model utilizes the MMTV-LTR to drive expression of the polyomavirus middle T-antigen in mammary glands, resulting in rapid development of highly metastatic tumors.
Which of the following cell lines is mentioned as an example of a metastatic mouse mammary carcinoma cell line?
Answer: 4T1
Exemplary metastatic mouse mammary carcinoma cell lines utilized for identifying genes and pathways involved in metastasis include 4T1 and TS/A, which exhibit metastatic behavior in syngeneic immunocompetent mice.
How does the Mouse Mammary Tumor Virus (MMTV) contribute to breast cancer models?
Answer: It acts as a promoter that can induce breast tumors when activated.
The Mouse Mammary Tumor Virus (MMTV) functions as a promoter, particularly its Long Terminal Repeat (LTR), which can induce breast tumors upon activation, often via steroid-hormone-inducible transcription.
The MMTV-PyMT model is significant because it:
Answer: Is the most commonly used model for studying mammary tumor progression and metastasis.
The MMTV-PyMT model is significant as it is widely recognized as the most prevalent model for investigating the complex processes of mammary tumor progression and metastasis due to its rapid development of highly metastatic tumors.
The MMTV-HER2/neu model uses the MMTV-LTR to promote the expression of which oncogene?
Answer: ErbB2 (HER2)
The MMTV-HER2/neu model employs the MMTV-LTR to promote expression of the receptor tyrosine-protein kinase ErbB2 (HER2), an oncogene amplified in approximately 20% of human breast cancers.
What is the primary function of the MMTV-LTR in mouse mammary cancer models?
Answer: To facilitate steroid-hormone-inducible transcription.
The primary function of the Mouse Mammary Tumor Virus Long Terminal Repeat (MMTV-LTR) in mouse mammary cancer models is to act as a promoter that facilitates steroid-hormone-inducible transcription, thereby controlling the expression of oncogenes within mammary epithelial cells.
What is the significance of fusing the mouse neu gene with the rat neu gene in the MMTV-HER2/neu model?
Answer: It improves the model's accuracy in representing HER2 gene amplification.
Fusing the mouse neu gene with the rat neu gene in the MMTV-HER2/neu model enhances its accuracy in representing HER2 gene amplification, leading to a more faithful recapitulation of the human disease phenotype.
Which of the following is an example of a gene whose acute ablation in MMTV-PyMT mammary tumor cells led to a significant increase in lung metastasis, identifying it as a regulator of metastatic behavior?
Answer: TGF-β1
Acute ablation of TGF-β1 signaling in MMTV-PyMT mammary tumor cells resulted in a significant increase in lung metastasis, identifying TGF-β1 as a key regulator of metastatic behavior in this model.
In K14-Cre BRCA2 mice, a mutation in p53 would simplify the determination of the tumor's origin.
Answer: False
In K14-Cre BRCA2 mice, a mutation in p53 would complicate the determination of the tumor's origin, as it introduces an additional genetic event that could obscure the primary cause or lineage.
For studying metastasis, tumor cells are commonly transplanted into immunocompetent mice.
Answer: False
For studying metastasis, particularly xenografts of human cells, tumor cells are commonly transplanted into immunodeficient mice to prevent rejection of the foreign tissue. Immunocompetent mice are typically used for syngeneic mouse-to-mouse transplants.
NOD/SCID mice are used for xenograft tissue integration because their intact immune systems promote robust foreign tissue acceptance.
Answer: False
NOD/SCID mice are used for xenograft tissue integration precisely because of their severely compromised immune systems, which allow for the integration and growth of foreign (human) tissue without rejection.
Mammary fat pads are 'humanized' by injecting human mammary epithelial cells to prepare them for tumor transplantation.
Answer: False
Mammary fat pads are typically 'humanized' by injecting human mammary fibroblasts or stromal cells, which then support the colonization and growth of human mammary epithelial cells for tumor transplantation. Direct injection of epithelial cells is not the standard humanization method.
A basic transgene typically consists of a promoter region, a protein-coding sequence, an intron, and a stop codon.
Answer: True
A fundamental transgene typically comprises a promoter region, a protein-coding sequence, an intron, and a stop codon.
Bi-transgenic mouse models contain only one transgene, allowing for the study of single gene effects.
Answer: False
Bi-transgenic mouse models, by definition, contain two transgenes, allowing for the study of gene interactions or combined effects, rather than solely single gene effects.
Inducible bi-transgenic models can be generated using tetracycline-controlled transcriptional activation, such as combining the Ras gene with rtTA.
Answer: True
Inducible bi-transgenic models are generated by combining genes like Ras with rtTA (reverse tetracycline transactivator). For instance, mice with TetO-KrasG12D and MMTV-rtTA transgenes allow for tetracycline-controlled expression of rtTA in mammary epithelial cells.
Lineage tracing in metastasis models is a strategy to resolve cell fates, requiring a switch (like Cre-recombinase) and a reporter transgene.
Answer: True
Lineage tracing in metastasis models is a quantitative strategy for resolving cell fates, requiring two engineered genomic components: a switch (e.g., drug-regulated Cre-recombinase) and a reporter transgene for cell identification.
Which of the following is a common method for generating mouse models of human breast cancer?
Answer: Targeted expression of oncogenes in mouse mammary epithelial cells.
Two principal methods for generating mouse models of human breast cancer include the targeted expression of oncogenes within mammary epithelial cells and the targeted inhibition of tumor suppressor genes.
What issue arises when studying tumorgenesis in K14-Cre BRCA2 mice if p53 is also mutated?
Answer: It becomes difficult to definitively determine the origin of the tumor.
In K14-Cre BRCA2 mice, concurrent p53 mutation complicates tumorgenesis studies by making it difficult to definitively ascertain the tumor's origin.
What is the common practice for transplanting tumor cells to study metastasis in immunodeficient mice?
Answer: Xenographic transplants of human cells into immunocompromised murine recipients.
Tumor cells are transplanted into immunodeficient mice via allotransplants or xenographic transplants, with human cells commonly inoculated into immunocompromised murine recipients.
Which inoculation route is specified for targeting the lung for metastasis in mice?
Answer: Tail vein injection
The tail vein injection route is specified for targeting the lung for metastasis in mice, as circulating cells injected via this route are readily trapped in the pulmonary vasculature.
Why are NOD/SCID mice utilized for xenograft tissue integration in breast cancer metastasis studies?
Answer: Their mutations allow for the integration of new xenograft tissue.
NOD/SCID mice, characterized by severe combined immunodeficiency, are employed for xenograft tissue integration in breast cancer metastasis studies due to their capacity to accept foreign tissue integration.
What is the purpose of 'humanizing' the mammary fat pads in NOD/SCID mice before tumor transplantation?
Answer: To enable human mammary epithelial cells to colonize and grow.
Humanizing the mammary fat pads, typically with human fibroblasts, is performed to create a supportive microenvironment enabling human mammary epithelial cells to colonize and proliferate, thereby facilitating successful tumor transplantation and subsequent metastasis studies.
Which of the following is a method used to construct genetically engineered mice for studying metastasis?
Answer: Introducing transgenes via tetracycline-inducible systems (Tet-On/Tet-Off).
Genetically engineered mice for metastasis studies can be constructed via transgenes introduced through tetracycline-inducible systems (Tet-On/Tet-Off), targeted mutations via Cre-Lox recombination (knock-in/knock-out), retroviral mutations, or chemical mutagenesis.
What is a characteristic of bi-transgenic mouse models?
Answer: They contain two transgenes.
Bi-transgenic mouse models are characterized by the presence of two distinct transgenes, which allows researchers to investigate the interplay between different genetic elements in disease development.
How can gene expression be controlled in tri-transgenic mouse models?
Answer: Activated at different time points using tetracycline operators.
Gene expression in tri-transgenic mouse models can be regulated for continuous expression or controlled temporal activation, often using tetracycline operators for genes like Myc and Ras, which respond to doxycycline.
What is lineage tracing in metastasis models designed to achieve?
Answer: To resolve cell fates.
Lineage tracing in metastasis models is a quantitative strategy for resolving cell fates, requiring two engineered genomic components: a switch (e.g., drug-regulated Cre-recombinase) and a reporter transgene for cell identification.
What is the purpose of using reporter genes like Beta-actin GFP or RFP in metastasis models?
Answer: To label cells for observation and tracking.
Reporter genes, such as Beta-actin GFP or RFP, are utilized in metastasis models to label specific cells, enabling their observation, tracking, and quantification throughout the metastatic process.
What are the two engineered components typically required for lineage tracing in metastasis models?
Answer: A switch (like Cre-recombinase) and a reporter transgene.
Lineage tracing in metastasis models is a quantitative strategy for resolving cell fates, requiring two engineered genomic components: a switch (e.g., drug-regulated Cre-recombinase) and a reporter transgene for cell identification.
Bioluminescence imaging detects light produced by the enzymatic oxidation of a substrate, typically luciferin, in the presence of luciferase.
Answer: True
Bioluminescence imaging detects light generated by the enzymatic oxidation of a substrate (e.g., luciferin) by luciferase. Systems like IVIS capture this light. For instance, in the MMTV-PyMT:IRES:Luc model, bioluminescence in the lungs post-doxycycline exposure indicates tumor cell presence.
Fluorescent imaging, particularly intravital microscopy, allows for the visualization of genetically engineered cells directly within a living organism.
Answer: True
Fluorescent imaging, especially intravital microscopy employing multi-photon excitation, enables direct visualization of genetically engineered cells within living organisms. Multi-step metastatic cascades can be observed by labeling cells with distinct fluorescent colors.
MRI imaging for metastasis studies uses nanoparticles containing a gadolinium contrast agent, which accumulate in areas where cells have metastasized.
Answer: True
MRI imaging for metastasis studies employs nanoparticles, often liposomes with gadolinium contrast agents. Injected into mice with metastases, these nanoparticles accumulate in metastatic sites, allowing detection via MRI scans.
How does bioluminescence imaging (BLI) detect tumor presence in mouse models?
Answer: By detecting light produced by the enzymatic oxidation of a substrate (e.g., luciferin) in the presence of luciferase.
Bioluminescence imaging detects light generated by the enzymatic oxidation of a substrate (e.g., luciferin) by luciferase. Systems like IVIS capture this light.
Which radioisotopic imaging technique is used to compare the efficiency of detecting lesions at an early stage and evaluate chemotherapy response?
Answer: PET, SPECT, and CT
Radioisotopic techniques like Positron Emission Tomography (PET), Single Photon Emission Computed Tomography (SPECT), and Computed Tomography (CT) are employed to assess early lesion detection efficiency and evaluate chemotherapy response in metastatic mouse models.
Mice are useful models for human diseases primarily because their genomes are significantly different from human genomes, allowing for unique studies.
Answer: False
Mice are useful models for human diseases primarily due to significant similarities in their physiology, development, and cell biology to humans, rather than differences. These shared characteristics facilitate the study of conserved biological processes.
A limitation of mouse models is the difficulty in precisely determining the exact location and frequency of metastasis.
Answer: True
Limitations in mouse models for breast cancer research include challenges in precisely determining metastasis location and frequency, and difficulties in specifically targeting epithelial subtypes during genetic manipulation.
Circulating tumor cells (CTCs) are difficult to study in live animals due to the high volume of peripheral blood that can be obtained.
Answer: False
Circulating tumor cells (CTCs) are difficult to study in live animals primarily due to the low volume of peripheral blood that can be obtained, which often results in a scarcity of CTCs for robust analysis, especially when specific markers are absent.
What is a key similarity between human and mouse genomes that makes mice useful models for human diseases?
Answer: Mice share close similarities in physiology, development, and cell biology with humans.
Mice serve as valuable models for human diseases due to profound similarities in physiology, development, and cell biology. They share approximately 30,000 protein-coding genes, with over 90% having human homologs, and exhibit high genomic synteny, with 40% alignable at the nucleotide level.
Which of the following is identified as a limitation of using mouse models for breast cancer research, particularly concerning metastasis?
Answer: Lack of precision in determining the exact location and frequency of metastasis.
Limitations in mouse models for breast cancer research include challenges in precisely determining metastasis location and frequency, and difficulties in specifically targeting epithelial subtypes during genetic manipulation.
What is a limitation in studying circulating tumor cells in live animals?
Answer: The low volume of peripheral blood that can be obtained.
A primary limitation in studying circulating tumor cells (CTCs) in live animals is the restricted volume of peripheral blood obtainable, which curtails the technique's applicability, particularly in the absence of specific mammary cell markers.