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Par trichard le 19 Janvier 2009 à 13:23Published online: 27 November 2008
Subject Categories:
Cancer induction by restriction of oncogene expression to the stem cell compartment
EMBO OpenMaría Pérez-Caro1, César Cobaleda2, Inés González-Herrero1, Carolina Vicente-Dueñas1, Camino Bermejo-Rodríguez1, Margarita Sánchez-Beato3, Alberto Orfao4, Belén Pintado5, Teresa Flores6, Manuel Sánchez-Martín7, Rafael Jiménez2, Miguel A Piris3 & Isidro Sánchez-García1
Received 24 June 2008; Accepted 7 November 2008
Abstract
In human cancers, all cancerous cells carry the oncogenic genetic lesions. However, to elucidate whether cancer is a stem cell-driven tissue, we have developed a strategy to limit oncogene expression to the stem cell compartment in a transgenic mouse setting. Here, we focus on the effects of the BCR-ABLp210 oncogene, associated with chronic myeloid leukaemia (CML) in humans. We show that CML phenotype and biology can be established in mice by restricting BCR-ABLp210 expression to stem cell antigen 1 (Sca1)+ cells. The course of the disease in Sca1-BCR-ABLp210 mice was not modified on STI571 treatment. However, BCR-ABLp210-induced CML is reversible through the unique elimination of the cancer stem cells (CSCs). Overall, our data show that oncogene expression in Sca1+ cells is all that is required to fully reprogramme it, giving rise to a full-blown, oncogene-specified tumour with all its mature cellular diversity, and that elimination of the CSCs is enough to eradicate the whole tumour.
Keywords:
- cancer,
- cancer stem cells (CSCs),
- CSC inhibitors,
- drug discovery,
- mouse models
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Par trichard le 19 Janvier 2009 à 13:08
http://www.nature.com/news/2009/090114/full/news.2009.23.html
Published online 14 January 2009 | Nature | doi:10.1038/news.2009.23
Genetic 'clock' made in lab
Synthetic metronome keeps time inside mammalian cells.
Swiss scientists have designed the genetic circuitry for a synthetic 'clock', inserted it into mammalian cells and used it to control the levels of a fluorescent protein.
The approach, which involves plugging genes together to create circuits not seen in nature, could allow scientists to one day make synthetic cellular metronomes that release drugs in precisely timed bursts.
It will also help scientists to understand natural 'oscillators', such as those that control our sleepwake cycle. "We were fascinated by these timekeeping devices and thought, to better understand them, we'd design a synthetic oscillator that acts like a natural one but has been composed of artificial components," explains Martin Fussenegger of the Swiss Federal Institute of Technology (ETH Zurich) in Basel, Switzerland, whose team carried out the experiments.
Such cellular timekeepers have been made to work inside bacterial cells1, but in more complex mammalian cells, the genetic networks have proven difficult to design.
Fussenegger and his colleagues have now managed to make an oscillator that turned the production of a fluorescent protein on and off in a hamster ovary cell and kept the cycle going for more than 20 hours2.
Making sense
As in previous approaches, the team took advantage of the genetic process of transcription, whereby a gene gets read out into the message that is then translated into a protein. Every gene actually consists of two pieces of DNA that are complementary to each other. If a gene is read forwards called 'sense' transcription the protein is generated in the normal way, but if the other, complementary strand is transcribed called antisense no protein is made.
The circuit results in the cyclical expression of a fluorescent protein inside cells.NatureThe circuit consists of bits of genetic code that order sense and then antisense transcription to be performed. The circuit also includes a sequence that makes green fluorescent protein so the team can easily tell if the circuit is working once it is inside a cell.
The circuit's starting sequence makes a protein called tTA, which does two things: it turns on the gene that makes green fluorescent protein, and another gene that makes a different compound, called PIT. PIT eventually shuts down the production of tTA until there's almost none left. The lack of tTA also means that PIT is no longer produced, and that allows the whole cycle to reset, with tTA production starting up again.
The team were also able to 'tune' the oscillator: inserting more of the genetic cassettes encoding the circuit increased the frequency of the oscillations; fewer decreased them. Their results are reported in Nature.
Time tool
Modelling oscillators and interfering with them also gives scientists insight into how nature's own metronomes work. "The problem with natural components is that they're inherently complicated and tied into the rest of a system," says Jeff Gore at the Massachusetts Institute of Technology in Cambridge, who has worked on similar projects in the past. "With synthetic systems you can make sure you really understand what's going on."
Such circuits may also have therapeutic potential in the future for example by regulating the levels of a particular protein or drug in the body. "One thing we are dreaming of is to have an oscillator express a protein such as insulin, and have it expressed every, say, six hours," says Fussenegger. "So we have an oscillator that could be not only a timekeeping device but also a kind of molecular production system."
Gore cautions that these applications are still far away but that this paper and other recent results have moved the field forwards. "Until it's built, you can't really say you understand it," he says.
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References
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Par trichard le 10 Décembre 2008 à 11:34http://www.inrp.fr/Acces/biotic/morpho/html/paroi.htm
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Par trichard le 10 Décembre 2008 à 11:30
Roger PRAT, Michèle MOSINIAK, Jean-Claude ROLAND
La paroi constitue un des éléments essentiels de la cellule végétale. Lorsque la cellule est jeune, sa paroi est appelée paroi primaire. Cette paroi est le lieu des échanges intercellulaires. Elle donne à la cellule sa forme et ses caractéristiques structurales. Elle permet également sa croissance. Ce document concerne essentiellement les aspects structuraux de la paroi primaire.
Rôles de la paroi Ultrastructure Les aspects physiologiques sont développés dans un autre document :
comment la cellule végétale grandit-elle?
http://www.snv.jussieu.fr/bmedia/paroi/index.htm#haut
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Par trichard le 10 Décembre 2008 à 11:12
Les organismes végétaux et particulièrement les plantes à fleurs se distinguent de la plupart des organismes animaux par des caractères remarquables. Ces plantes sont pratiquement immobiles et fixées dans le sol. En conséquence, elles sont tributaires du milieu qui les entoure. Les plantes à fleurs ont pourtant conquis l'ensemble du milieu terrestre et ceci grâce à quelques caractéristiques.
En premier lieu, la PhotosynthèseRéaction se déroulant chez les plantes dans les chloroplastes où l\'énergie solaire est utilisée pour oxyder l\'eau et réduire le gaz carbonique afin de synthétiser des substances organiques (glucides).');" onmouseout="killlink()">photosynthèse leur permet de trouver directement dans l'AtmosphèreCouche gazeuse qui enveloppe certaines planètes. Sans notre atmosphère, nous ne pourrions vivre sur Terre. En astronomie, enveloppe gazeuse entourant un corps céleste et pouvant contenir des particules en suspension (poussières, gaz, aérosols...). Les étoiles ont toutes une atmosphère gazeuse dont...');" onmouseout="killlink()">atmosphère la source de CarboneElément chimique non-métallique (symbole C), de numéro atomique 6, de masse atomique 12,01, appartenant au groupe 14 de la classification de Mendeleev, de valence 4.
Le corps simple, de point d\'ébullition 3550°C, de point de fusion 4827°C, existe à l\'état solide sous trois formes cristallines :...');" onmouseout="killlink()">carbone nécessaire à la synthèse de leurs MoléculeEnsemble d\'atomes unis les uns aux autres par des liaisons chimiques.');" onmouseout="killlink()">molécules organiques. En deuxième lieu, l'acquisition d'un port dressé, d'un système d'AbsorptionPHYSIQUE Phénomène par lequel une partie de l\'énergie de rayonnements électromagnétiques ou corpusculaires est dissipée dans un milieu matériel.
PHYSIOLOGIE Pénétration d\'une substance venant de l\'extérieur dans un organisme vivant. Absorption intestinale : passage des substances nutritives de...');" onmouseout="killlink()">absorption d'eau directement dans le sol et de divers systèmes de régulation des pertes d'eau leur permet de résister à des conditions momentanées ou saisonnières parfois difficiles.
Figure 1 Arbre majestueux.
La solidité de son tronc, de ses branches et de ses racines lui permet d'occuper un espace important dans le sol et l'atmosphère. Son feuillage et ses racines lui assurent sa nutrition et en hiver, la chute de ses feuilles lui permet de résister aux mauvaises conditions.Ces caractères structuraux et physiologiques de ces organismes dépendent en fait étroitement des caractères originaux de leurs cellules.
- La cellule végétale
- Généralités
- La vacuole
- Composition et architecture de la paroi primaire
- La paroi et la morphogenèse cellulaire
- Division cellulaire et communications intercellulaires
- Croissance des cellules végétales jeunes
- Structure des chloroplastes
- Chloroplastes et photosynthèse
- Les amyloplastes
http://www.futura-sciences.com/fr/doc/t/botanique/d/la-cellule-vegetale_439/c3/221/p1/
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