Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
The contribution of tumorigenic stem cells to haematopoietic cancers has been established for some time, and cells possessing stem-cell properties have been described in several solid tumours. Although chemotherapy kills most cells in a tumour, it is believed to leave tumour stem cells behind, which might be an important mechanism of resistance. DORMANT METASTASES...the first evidence Chemotherapy and cycling cells Thus, stem cells do not cycle markers Figure 3. Expression of CD34 on expanded cells Summers, Y. J. et al. Stem Cells 2001;19:505-513 Copyright ©2001 AlphaMed Press Nude mice/SCID mice La frontiera delle IPS Figure 1. Generation of iPS Cells from MEF Cultures via 24 Factors(A) Strategy to test candidate factors.(B) G418-resistant colonies were observed 16 days after transduction with a combination of 24 factors. Cells were stained with crystal violet.(C) Morphology of ES cells, iPS cells (iPS-MEF24, clone 1-9), and MEFs. Scale bars = 200 μm.(D) Growth curves of ES cells, iPS cells (iPS-MEF24, clones 2-1–4), and MEFs. 3 105 cells were passaged every 3 days into each well of sixwell plates.(E) RT-PCR analysis of ES cell marker genes in iPS cells (iPSMEF24, clones 1-5, 1-9, and 1-18), ES cells, and MEFs. Nat1 was used as a loading control.(F) Bisulfite genomic sequencing of the promoter regions of Oct3/4, Nanog, and Fbx15 in iPS cells (iPS-MEF24, clones 1-5, 1-9, and 1-18), ES cells, and MEFs. O II. Rapporto tra ciclo e differenziamento • • • • Mantenimento in ciclo Uscita dal Ciclo Differenziamento Apoptosi • Senescenza Figure 17-1 Molecular Biology of the Cell (© Garland Science 2008) FACS profili BRDU per marcare cellule in fase S models Figure 17-4 Molecular Biology of the Cell (© Garland Science 2008) history • Nurse, Hunt & Hartwell • The Nobel Prize in Physiology or Medicine 2001 • "for their discoveries of key regulators of the cell cycle" Inaugural Speech Presentation • • • • • • • • • Cell division is a fundamental process of life. All living organism on earth are descended from an ancestral cell that appeared about 3 billion years ago, and which has undergone an unbroken series of cell divisions since then. Each human being also began life as one single cell - a cell that divided repeatedly to give rise to all one hundred thousand billion cells that we consist of. Every second millions of cells divide in our body. The cycle of events that a cell completes from one division to the next is called the cell cycle. During the cell cycle the cell grows in size, it duplicates its hereditary material - that is, it copies the DNA molecules in the chromosomes - and it divides into two daughter cells. This year's Nobel Laureates have discovered the key regulators of the cell cycle, cyclin dependent kinase (CDK) and cyclin. Together these two components form an enzyme, in which CDK is comparable to a "molecular engine" that drives the cell through the cell cycle by altering the structure and function of other proteins in the cell. Cyclin is the main switch that turns the "CDK engine" on and off. This cell cycle engine operates in the same way in such widely disparate organisms as yeast cells, plants, animals and humans. How were the key regulators CDK and cyclin discovered? Lee Hartwell realized the great potential of genetic methods for cell cycle studies. He chose baker's yeast as a model organism. In the microscope he could identify genetically altered cells - mutated cells - that stopped in the cell cycle when they were cultured at an elevated temperature. Using this method Hartwell discovered, in the early 1970s, dozens of genes specific to the cell division cycle, which he named CDC genes. One of these genes, CDC28, controls the initiation of each cell cycle, the "start" function. Hartwell also formulated the concept of "checkpoints," which ensure that cell cycle events occur in the correct order. Checkpoints are comparable to the program in a washing machine that checks if one step has been properly completed before the next can start. Checkpoint defects are considered to be one of the reasons behind the transformation of normal cells into cancer cells. Paul Nurse also used the genetic approach in his cell cycle studies, but in a different kind of yeast. In the late 1970s and early 1980s he discovered the gene cdc2, which could be mutated in two different ways. Either the cells did not divide, or they divided too early. From this he correctly concluded that cdc2 controls cell division. He later discovered that cdc2 not only controls cell division, the final event of the cell cycle, but has a key regulatory function for the whole cell cycle, including that described for CDC28 in baker's yeast. This key function was shown to be that of CDK in the cell cycle engine. By moving human genes into yeast cells, in 1987 Nurse isolated a human cdc2 gene. This human cdc2 gene functioned perfectly in yeast cells. Thus, the CDK function in the cell cycle engine had been concerved through more than one billion years of evolution - from yeast to man. Tim Hunt discoverd the other key component of the cell cycle engine, the protein cyclin, which regulates the function of the CDK molecule. Working with sea urchin eggs as a model organism, in 1982 he discovered a specific protein that increased in amount before cell division but disappeared abruptly when the cells divided. Because of these cyclical variations, he named the protein cyclin. These experiments not only led to the discovery of cyclin, but also demonstrated the existence of periodic protein degradation in the cell cycle - a fundamental control mechanism. Hunt also showed the existence of cyclins in other, unrelated species. Thus cyclins, like CDK, had been conserved during evolution. It is now almost fifty years since the structure of the DNA molecule - the double helix - was discovered, leading to a molecular explanation of how a gene can make a copy of itself. With the discoveries of CDK and cyclin we are now beginning to understand, at the molecular level, how the cell can make a copy of itself. Dr. Hartwell, Dr. Hunt and Dr. Nurse. Your fundamental discoveries have profoundly increased our understanding of how the cell cycle is controlled. This new knowledge has a huge impact on cell biology with broad applications in many fields of biology and medicine. CHECKPOINTS Figure 17-21 Molecular Biology of the Cell (© Garland Science 2008) Figure 17-3 Molecular Biology of the Cell (© Garland Science 2008) Figure 17-43 Molecular Biology of the Cell (© Garland Science 2008) PROTEOLISI • add Ricorda! Li Fraumeni Syndrome ed arresto del ciclo p53 Struttura di p53, identifica una proteina multimodulare here Struttura di p53 sul DNA Figure 17-63 Molecular Biology of the Cell (© Garland Science 2008) here