Lecture 22 Outline of Last Lecture I. Split Genes and RNA ProcessingII. MicroRNAs and Gene ExpressionIII. MutationsIV. VirusesV. Types of VirusesOutline of Current Lecture I. CancerII. Oncogenes and Proto-OncogenesIII. Tumor-Suppressor GenesIV. MicroRNAsCurrent LectureMolecular Biology of Cancer CellsI. Cancera. Definition – set of diseased in which cells escape the control mechanisms that normally limit celldivisionb. It is associated with mutations that affect gene expressionc. Often many mutations in different genes are needed to produce all of the characteristics of cancerd. Altered expression of mircoRNAs is commone. Two major classes of protein-coding genes are mutated or have altered expression in canceri. Oncogenes or proto-oncogenesii. Tumor-suppressor genesII. Oncogenes and Proto-Oncogenesa. Onco = Greek for tumorb. Certain retroviruses causes cancer because they have oncogenes that promote cell divisionc. “Proto-oncogenes” - normal cells found to have genes similar to viral oncogenes i. Genes that can cause cancer if expressed at too high level or without proper controls BIOL 1st Editionii. Example: RAS a signaling protein that turns on cell cycle in response to growth factors– in cancer RAS signaling occurs all the time, even in the absence of growth factord. RAS is mutated in 30% of human cancersIII. Tumor-Suppressor genesa. Normal product inhibits cell divisionb. A mutation that decreases the normal activity of a tumor-suppressor may contribute to cancerc. Example: P53 “guardian angel of the genome” i. DNA damage turns on P53 expressionii. P53 is a transcription factor that turns on P21iii. P21 decreased the cell cycles, thus allowing time to repair DNAiv. If DNA damage is too much, P53 tunes on a process called “apoptosis” – cell suicided. P53 is mutated in 50% of cancersIV. MicroRNAsa. Small RNAs that are master regulators of cell divisionb. Tumor-suppressor miRNAs – promising therapy to cancer i. Some miRNAs are lost in cancer cellsii. Tumor-suppressor miRNAs replace the miRNAs that are lost, and block the cancerc. “Oncogenic miRNAs” (onco-miRs) miRNAs that are over-expressed in cancer and promote
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