1NAME_______________________________________________TA________7.013 Spring 2005 Problem Set 6FRIDAY April 29th, 2005Problem sets will NOT be accepted late.Question 1You are given the following cancer cell line derived from a patient’s cervical tumor. Your job tocharacterize what caused the tumor in this cell line. You compare this cell line to a cell linederived from the same patient’s normal cervical cells.Normal Cervical Cella) First you expose the two cell lines to DNA damaging UV radiation and look at the effects. Youfind that normal cervical cells die after UV exposure, but the cancer cells do not. Which of thefollowing are suggested by this experiment? Circle all that apply.i) a tumor suppressor gene is mutated in this tumor.ii) an oncogene is mutated in this tumor.iii) a gene involved in apoptosis is mutated in this tumor.iv) a gene involved in DNA repair protein is mutated in this tumor.v) a gene involved in metastasis is mutated in this tumor.vi) a gene involved in angiogenesis is mutated in this tumor.b) You look at the location of commonly known cancer genes in the two cell lines by analyzinggenetic markers and you determine that there is a loss of heterozygosity on chromosome 13 onlyin the cancer cells. Using a virus you introduce a wild-type copy of a gene from chromosome 13known to be involved in carcinogenesis into the cancer cell line.You find that introduction of this gene copy slows down the rate of cell division in the cancer line.Cervical Cancer cellgene fromChromosome 13MIT Department of Biology7.013: Introductory Biology - Spring 2005Instructors: Professor Hazel Sive, Professor Tyler Jacks, Dr. Claudette Gardel2Which of these hypotheses is suggested by this observation? (Circle all that apply.)Chromosome 13 contains...i) an apoptotic factor that is mutated in the cancer cell line.ii) an oncogene that is mutated in the cancer cell line.iii) a tumor suppressor gene that is mutated in the cancer cell line.iv) a gene coding for a DNA repair protein that is mutated in the cancer cell line.v) a gene required for metastasis.vi) a gene required for angiogenesis.c) A colleague discovered a gene that is mutated in late-stage (aggressive) cervical tumors. Hegives you a vector containing a wildtype copy of this gene that you transfect into your originalcervical cancer cell line. You observe no differences in growth, cell death or any other propertiesin standard tissue culture tests.You inject these transfected cells, as well as the original cancer cell line (not transfected) intodifferent groups of mice. You observe...• Primary Tumors of similar size develop in both groups of mice.• The original cancer cell line kills all the mice within 2 month of transfection and dissectionof these mice show tumors throughout body.• The transfected cancer cell line does not kill the mice within the 6 months of transfection.Which hypotheses are suggested by these observations?The gene codes for a protein that...i) inhibits cell division.ii) promotes cell division.iii) prevents apoptosis.iv) prevents metastasis.v) repairs DNA.vi) promotes angiogenesis.3e) Since Human Papilloma Virus (HPV) infection is associated with cervical cancer, you obtain aHPV-infected cancer cell line and a corresponding uninfected normal cell line from a patient. Youdetermine that there is no p53 protein in the infected cancer cells, although the RNA isexpressed normally.When you infect the normal cell line with HPV, you find that the p53 protein levels dropdramatically, yet the p53 RNA levels remain the same. Which of the following could explain howHPV might be involved in cervical cancer.i) HPV causes the degradation of the p53 protein.ii) HPV codes for an oncogene that is expressed at high levels.iii) HPV integrates into p53 locus, thereby knocking out the p53 gene.iv) HPV promotes tumorigenisis by suppressing the immune system of the infected patient.v) HPV codes for a protein that degrades a DNA repair protein, leading to mutations in the p53gene.vi) HPV encodes a p53 gene to be expressed at high levels.e) Your colleague has come up with an idea to devise a gene therapy for cervical cancers with HPV.His idea is to introduce a wild-type copy of the gene encoding the p53 gene into the HPV infectedcancer cells. Will this work?? Explain why or why not.f) Iressa is a drug that was recently designed to inhibit the EGF signaling pathway. If youwere to discover that adding Iressa to cancer cells from some tumors killed themimmediately, what might you suspect about EGF signaling in these tumors? Choose thebest answer.i) EGF receptor signaling in these cancer cells is needed for the cells to divide.ii) EGF receptor signaling in these cancer cells prevents apoptosis.iii) EGF receptor signaling in these cancer cells promotes cell growth and apoptosis.iv) EGF receptors from these cancer cells bind to Iressa, leading to increased EGF receptorsignaling.4g) In the final stages of generating Iressa, investigators performed a battery of tests tocompare various versions (a, b, c, and d) of the drug to find one with all the propertiesnecessary for effective therapy. Shown below are two of the tests performed. Giventhat low concentrations and long duration of effective dose in the blood are most criticalin choosing a drug, from these tests, which compound would you choose as your drug?i) drug aii) drug biii) drug civ) drug dv) all drugs are equally effective.5Question 2You are biking along Mass Ave, enjoying the weather and watching the teeming masses ofprospective students. Amidst your nostalgia, you fail to notice a car-sized pothole, take a roughfall, and end up with a nasty cut on your left knee.a) Over the course of several hours, the cut gradually swells up and becomes red and tender. You concludethat cells from your immune system are being recruited to the site of injury by cytokines such asinterleukins and other messenger molecules. Circle the predominant white blood cell type(s) entering theinjury region at this time.B-cells CD4+ Helper T-cells CD8+ Killer T-cells Macrophages Mast Cells Neutrophils NoneTwo days after the initial injury, the cut is still red and swollen, as a result of white blood cellsleaving the bloodstream and entering the tissues at the injury site. This is normally caused bypro-inflammatory cytokines that bind to receptors on the endothelial cells lining nearby bloodvessels, causing these cells to express integrin. When integrin binds its receptor the white
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