Term
| True or False: In vivo experiments take place outside the organism (or cell). |
|
Definition
| 1) False: In vivo experiments take place WITHIN the organism (or cell). |
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Term
| In vivo requires understanding on what aspects? |
|
Definition
1) Nutritional state of animal
2) Hormone levels
3) Endogenous infections
4) Determination of which cells play a critical role in transformation in mixtures of cell types |
|
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Term
| Cultured cells are defined and can be manipulated, but what 4 criteria (questions) should be met (answered) before proceeding in vivo? |
|
Definition
1) Do they represent the transformed phenotype?
2) What are the essential properties of the malignant state?
3) Any phenotypic and genotypic changes after several passages in culture?
4) Can the cells produce a tumor in vivo? |
|
|
Term
| A characteristic of nude mice is that they lack what essential organ? |
|
Definition
| 1) A thymus (reason they are immunocompromised) |
|
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Term
| True or False: Nude mice lack a thymus and as a result are relatively receptive to engrafted cells from genetically related sources including cells from foreign species. |
|
Definition
| 1) False: Nude mic lack a thymus and as a result are relatively receptive to engrafted cells from genetically UNRELATED sources including cells from foreign species. |
|
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Term
| True or False: You can monitor tumor formation of a nude mice through injections under the skin. |
|
Definition
|
|
Term
| What are 6 characteristics of cultured transformed cells? |
|
Definition
1) Immortality (telomeres never shorten)
2) Decreased density-dependent contact inhibition
3) Decreased serum requirement
4) Loss of anchorage dependence
5) Altered cell surface properties
6) Altered display of enzyme patterns |
|
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Term
| As a cell transforms, it becomes more and more __________. |
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Definition
|
|
Term
| What are transcription factors (TFs)? |
|
Definition
| 1) Are sequence-specific DNA binding factors |
|
|
Term
| What are the role of transcription factors (TFs)? |
|
Definition
1) Modulate growth of normal cell activity
2) Multiple interactions allow for varying degrees of control over rates of transcription |
|
|
Term
| What is responsible for initiating cell-to-cell signaling? |
|
Definition
|
|
Term
| True or False: TFs recognize specific motifs which can be upstream or downstream from the promotor gene region. |
|
Definition
| 1) False: TFs recognize specific motifs which can be upstream or downstream from the GENE or ENHANCER region. |
|
|
Term
| How do TFs enhance the process of transcription? |
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Definition
| 1) TFs bind, attract other TFs, and create complex that facilitates binding by RNA polymerase. |
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Term
| In normal cell-to-cell signaling, each growth factor has what 3 essential components? What type of cell-to-cell signaling are these receptors involved in? |
|
Definition
1) An N-ectodomain
2) A transmembrane domain
3) A cytoplasmic C-domain
4) Physiological |
|
|
Term
| What are PDGFs? What is their source and where are they released? |
|
Definition
1) Platelet-derived growth factors (PDGFs) are platelet-derived growth factors that swarm a wound site to reconstruct the tissue (while attracting fibroblasts) during the wound healing process.
2) PDGFs are released by platelets during clotting. |
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|
Term
| True or False: If PDGFr is silenced reconstruction is possible. |
|
Definition
| False: If PDGFr is silenced reconstruction is IMPOSSIBLE |
|
|
Term
|
Definition
| 1) 170,000 molecular weight (mwt) glycoprotein with endogenous tyrosine kinase activity; binds to PDGF with high affinity. |
|
|
Term
| PDGFs can be found on what cells? |
|
Definition
1) Fibroblasts
2) Glial cells
3) Arterial SM cells
4) Other connective tissue cells |
|
|
Term
| What are the two primary characteristics of GFrs? |
|
Definition
1) Many are mitogenic members of families of receptor kinases with enzymatic activities in their catalytic domains
2) Many have been implicated in tumorigensis |
|
|
Term
| Compasrison of amino acid sequences within the __________ __________ of the EGFr reveal what about its structure? |
|
Definition
1) Cytoplasmic domain
2) There are areas of sequence homology with certain growth regulatory tryosine kinases like c-src involved in signaling cascades. |
|
|
Term
| The transmembrane and cytoplasmic domains of what two proteins are clostely related to each other? |
|
Definition
1) EGFr
2) V-erb-B oncoprotein |
|
|
Term
| What is the original source of the v-erb-b oncoprotein? |
|
Definition
| 1) Originally found in the genome of avian erythroblastsis virus |
|
|
Term
| What is the avian erythroblastosis virus? |
|
Definition
| 1) A transforming retrovirus that induces leukemia in avian erythroblasts |
|
|
Term
| What is the function of the v-erb-b oncoprotein? |
|
Definition
| 1) If a mutation results in a missing ectodomain where the ligand would normally bind, the receptor can send growth-stimulating signals into cells constitutively, and fully independent of the EGF, as an oncoprotein. |
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|
Term
| True or False: The v-erb-b oncoprotein can send growth-stimulating signals into cells fully dependent on the EGF if a mutation results in a missing ectodomain where a ligand would normally bind. |
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Definition
| False: The v-erb-b oncoprotein can send growth-stimulating signals into cells fully INDEPENDENT (as an oncoprotein) on the EGF if a mutation results in a missing ectodomain where a ligand would normally bind. |
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|
Term
| Mutations cause subtle change in __________ __________. |
|
Definition
|
|
Term
| Normal growth factor receptors often emit what in response to ligand binding? |
|
Definition
| 1) A controlled cytoplasmic signal |
|
|
Term
| True or False: Mutations maintain regulated signals and alterations in cell signaling. |
|
Definition
| 1) False: Mutations yield DEREGULATED signals and alterations in cell signaling. |
|
|
Term
| What are 3 examples of mutations that may yield deregulated signals and alterations in cell signaling to normal growth factor receptors? |
|
Definition
1) Amino acid substitutions
2) Truncation of the ectodomain
3) Over-expression |
|
|
Term
| True or False: Sometimes, mutations in the growth factor itself can lead to autocrine transformation |
|
Definition
|
|
Term
| What oncogene similar to the v-erb-b was found in simian sarcoma virus? |
|
Definition
|
|
Term
| What is the source of the v-sis oncogene? |
|
Definition
|
|
Term
| What is the v-sis oncogene? |
|
Definition
| 1) A retroviral homolog of the cellular gene encoding beta chain of PDGF (c-sis) |
|
|
Term
| What oncogene is overexpressed in a large percentage of human tumor cells? |
|
Definition
| 1) c-sis/PDGF-beta proto-oncogene |
|
|
Term
| True or False: Human c-sis/PDGF-beta proto-oncogene is not expressed enough in a large percentage of human tumor cells? |
|
Definition
| 1) False: Human c-sis/PDGF-beta proto-oncogene is OVEREXPRESSED in a large percentage of human tumor cels |
|
|
Term
| When does the c-sis bind to the PDGFr |
|
Definition
| 1) As an oncogene, it binds to the PDGFr when displayed on the same cell (autocrine) |
|
|
Term
| What are the roles of the c-sis/PDGF-beta proto-oncogene? |
|
Definition
1) Binds to PDGFr when displayed on the same cell (autocrine)
2) Produces growth-promoting signals |
|
|
Term
| What occurs when a cogante receptor is expressed by cells? |
|
Definition
| 1) An auto-stimulatory or autocrine loop begins |
|
|
Term
| What does it mean for something to be cognate? |
|
Definition
| 1) If something is cognate, it is present in cell PM and normally under paracrine control |
|
|
Term
| What is the role of TGF-Alpha? |
|
Definition
| 1) Binding ligand for EGRr |
|
|
Term
| Autocrine Loop can be found in what type of carcinoma? |
|
Definition
| 1) Human breast carcinoma |
|
|
Term
| What factors influence Karposi's sarcoma? |
|
Definition
Originates from connective tissue cells that produce:
1) PDGF
2) TGF beta
3) IGF1
4) Cognate receptors for growth factors |
|
|
Term
| Karposi's sarcoma simultaneously being affected with with human virus forces infected cells to synthesize novel viral growth factors? |
|
Definition
|
|
Term
| __________ leads to a cascade of signaling in the cell's interior. |
|
Definition
|
|
Term
| What is autophosphorylation? |
|
Definition
| 1) Self stimulation of a single receptor's cytoplasmic domain |
|
|
Term
| What does the mechanism of autophosphorylation lead to? |
|
Definition
| 1) Transphorylation and a signaling cascade |
|
|
Term
| In transformed cells, efficiency of an aberrant signal response is dependent upon what? |
|
Definition
1) Over-expression in the number of receptors that can be dimerized
2) A diverse array of receptor structural alterations leading to dimerization in the absence of receptor over-expression |
|
|
Term
| What gene is the cousin of EGRr and is linked to breast cancer? |
|
Definition
|
|
Term
| A point mutation substitutes valine for what in receptor tryosine kinase domain? |
|
Definition
|
|
Term
| HER2/Nev (erb-b2) favors what two factors? |
|
Definition
1) Constitutive dimerization
2) Creation of potent oncoprotein |
|
|
Term
| What occurs with the increased presence of altered receptors? |
|
Definition
| 1) Increases the possibility of dimerization and aberrant signaling pathway. |
|
|
Term
| Receptors produced from fusion genes constitutively dimerize and can be found where? |
|
Definition
1) Hematological
2) Sarcomas
3) Prostate cancers |
|
|
Term
| How are fusion genes created? |
|
Definition
1) Chromosome translocation
2) Interstitial deletion
3) Chromosomal inversion |
|
|
Term
| True or False: In a number of benign tumors, growth factor receptors bond with other unrelated proteins, which naturally dimerize. |
|
Definition
| 1) False: In a number of MALIGNANT tumors, growth factor receptors bond with other unrelated proteins, which naturally dimerize. |
|
|
Term
| What occurs when proteins dimerize? |
|
Definition
| 1) Dimerization draws the ectodomains of receptors to each other resulting in receptor dimerization |
|
|
Term
| True or False: Often, a receptor protein can be fused to more than one fusion partner decreasing the possibility of dimerization. |
|
Definition
| 1) False: Often, a receptor protein can be fused to more than one fusion partner INCREASING the possibility of dimerization |
|
|
Term
| About how many genes are in our genome? |
|
Definition
|
|
Term
| Of the 22,000 genes in our genome, how many encode tryosine kinase receptors having general structures of EGFr and PDGFr as implicated in oncogenesis? |
|
Definition
|
|
Term
| Of the 22,000 genes in the human genome, only 58 encode tryosine kinase receptors having general structures of what receptors? |
|
Definition
|
|
Term
| True or False: A number of altered Tryosine Kinase GF receptors have been found in human tumors. |
|
Definition
|
|
Term
| True or False: Neoplasia initiated by viruses, with altered alpha NF receptors, respond well therapeutically. |
|
Definition
| 1) False: Neoplasia initiated by viruses, with altered alpha INF receptors, WON'T respond well therapeutically. |
|
|
Term
| Cytokine receptors do now contain what? |
|
Definition
| 1) Cytoplasmic kinase domains (autophosphorylate) |
|
|
Term
| What occurs when ligands bind to cytokine receptors? |
|
Definition
| 1) Associated kinase proteins (Tyk2 and Jak1) are activated and then transphosphorylate receptor domains |
|
|
Term
| C-terminal tails of receptor molecule emit signal cascades similar to what? |
|
Definition
| 1) Tryosine kinase receptors |
|
|
Term
| What is the role of TGFr beta? |
|
Definition
| 1) Imposes growth inhibition on cancer cells through repression of c-myc transcription |
|
|
Term
| Phosphorylation of serine and theronine resides rather than tryosine occurs where? |
|
Definition
|
|
Term
| What must occur to initiate receptor action and a signal cascade with growth factor receptors? |
|
Definition
| 1) Type II receptor cytodomains must phosphorylate Type I |
|
|
Term
| True or False: Mutant receptors won't dimerize removing antiproliferative activity. |
|
Definition
|
|
Term
| What is the role of integrin molecules? |
|
Definition
1) Function as heterodimeric transmembrane proteins
2) Function as receptors
3) Tether the cell to ECM and the cytoskeleton (inside the cell) |
|
|
Term
| What occurs when cancer cells have mutations in intergrin molecules? |
|
Definition
| 1) The mutations prevent the transformed cell from hinging to the ECM, aiding in spread from original site (metastases) |
|
|
Term
| How do epithelial tumors often grow? |
|
Definition
| 1) Slowly and remain localized (in situ) for many years |
|
|
Term
| What does it mean for cancer to remain in situ? |
|
Definition
|
|
Term
| What is tumor angiogenesis? |
|
Definition
| 1) Process in which growing tumors (which are ready to invade) will elicit new capillary growth from host |
|
|
Term
| What is another name of tumor angiogenesis? |
|
Definition
|
|
Term
| In breast carcinomas, tumors send out signals from tumor cells through the basement membrane to what new area? What is the result? |
|
Definition
1) Signals go to the stroma
2) Results in growth of small vessel that surround tumor mass |
|
|
Term
| Are the angiogenic signals sent from breast carcinomas able to penetrate the BM? Why or why not? |
|
Definition
1) No
2) The BM maintains integrity |
|
|
Term
| What is the main angiogenic molecule in angiogenesis? What happens if it is blocked? |
|
Definition
1) The VEGF
2) Reduces vascularization |
|
|
Term
| What are the 3 steps associated with the angiogenic switch mechanism |
|
Definition
1) Preangiogenic hyperplastic islet cells recruit mast cells and macrophages from bone marrow
2) Inflammatory cells release metalloproteinases in vicinity of tumor, degrading ECM around hyperplastic cells releasing VEGF
3) Solubilization and activation of VEGF induces angiogenic switch new vessel formation around islet |
|
|
Term
| How are the Islets of Langerhan cells sustained during the angiogenic switch? What occurs when an islet tumor expands? |
|
Definition
1) Sustained largely though diffusion from surrounding microvessels
2) During expansions, there is a dramatic increase in vessel formation around the tumor |
|
|
Term
| What occurs during carcinogenesis? |
|
Definition
| 1) A number of developmental genes are re-expressed, a phenomenon known as onco-developmental gene expression |
|
|
Term
| What are two developmental genes that are re-expressed during carcinogenesis? |
|
Definition
1) Alpha-fetoprotien (AFP)
2) Carcinoembryonic antigen (CEA) |
|
|
Term
| When is AFP normally produced? When is it abnormally produced? |
|
Definition
1) Produced by fetal live and yolk sac at 15 weeks gestation
2) Present in patients with embryonal testicular and hepatocellular carcinoma |
|
|
Term
| When is CEA normall produced? When is it abnormally produced? |
|
Definition
1) Produced at low levels in tissues with mucin-secreting epithelium to help in development of placenta
2) Increased production and shed into blood by carcinomas (and tumors of the digestive tract) |
|
|
Term
| True or False: Genetic mutations in transformed cells lead to phenotypic alterations. |
|
Definition
|
|
Term
| What are 4 consequences of genetic mutations that lead to phenotypic alterations? |
|
Definition
1) Alter cell-to-cell signaling
1A) Increased oncogenicity
1B) Decreased anti-proliferative ability
1C) Increased autonomy
2) Reduced cell-to-cell dependency
3) Increased neovascularization
4) Re-expression of oncodevelopmental proteins and dedifferentiated properties |
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