Caracterització i regulació transcripcional del gen "pfkfb3"
作者： Mercè Obach Cortadellas
DOI:
关键词:
摘要: Els resultats que es presenten en aquesta memoria aporten informacio ens permet donar un pas mes el coneixement de la regulacio transcripcional del gen pfkfb3 i consequentment via glucolitica. En primer lloc, hem localitzat els elements resposta HIF-1 al promotor observat aquests eren essencials per a hipoxia cellules glioblastoma huma (T98G) fibroblasts embrionaris ratoli (mEF). Seguidament, corroborat implicacio progesterona pfkfb3, inicialment havien descrit Hamilton collaboradors {Hamilton, 1997 #93}. Hem posat manifest laugment dexpressio duPFK-2 seu mRNA cancer mama (T47D) incubades amb hormona. A mes, determinat aquest increment era degut laccio dels receptors (PR, progesterone receptors). una possible sequencia consens (PRE, response element) pero encara no pogut demostrar si paper exerceix daquest nivell o destabilitzacio mRNA. Per comprovar obtinguts aillades, estudiat in vivo, utilitzant com model dexperimentacio animal soca ratolins C57/BL6. tractat STZ lincrement duPFK-2, concentracio Fru-2,6-P2 fetge danimals diabetics. Parallelament, realitzat lestudi tecnica transferencia genica hidrodinamia. demostren transcripcio diabetics condicions dejuni. estudis immunohistoquimics fetges controls, demostrant lexpressio produeix principalment hepatocits proliferants zona perivenosa Tambe les vies senyalitzacio porten PI3K/Akt/mTOR (activa aquestes altament proliferants) hi te essencial. Aquests sobre juntament ja shavien #93}; {Chesney, 1999 #96}; {Atsumi, 2002 #110}; {Riera, #113}; {Minchenko, #144}; 2003 #114}; {Bando, 2005 #102}; {Telang, 2006 #106}, confirmen importancia fenotip glucolitic tumorals. El controla sintesi que, sha explicat introduccio, lactivador allosteric potent lenzim PFK-1. Per tant, podem considerar clau glucolitica, manera augment diferents tipus tumorals condueix lactivacio daquesta i, consequentment, afavoreix canvi cap glucolitic.
unirioja.es参考文章(225)
Mercedes Pozuelo Rubio, Mark Peggie, Barry HC Wong, Nick Morrice, Carol MacKintosh, 14‐3‐3s regulate fructose‐2,6‐bisphosphate levels by binding to PKB‐phosphorylated cardiac fructose‐2,6‐bisphosphate kinase/phosphatase The EMBO Journal. ,vol. 22, pp. 3514- 3523 ,(2003) , 10.1093/EMBOJ/CDG363
Szkudelski T, The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas. Physiological Research. ,vol. 50, pp. 537- ,(2001)
J. V. Hunt, C. C. T. Smith, S. P. Wolff, Autoxidative glycosylation and possible involvement of peroxides and free radicals in LDL modification by glucose. Diabetes. ,vol. 39, pp. 1420- 1424 ,(1990) , 10.2337/DIAB.39.11.1420
Masayoshi Imagawa, Robert Chiu, Michael Karin, Transcription factor AP-2 mediates induction by two different signal-transduction pathways: protein kinase C and cAMP. Cell. ,vol. 51, pp. 251- 260 ,(1987) , 10.1016/0092-8674(87)90152-8
Jasmine Jacob-Hirsch, Yoel Kloog, Ninette Amariglio, Gideon Rechavi, Roy Blum, Ras Inhibition in Glioblastoma Down-regulates Hypoxia-Inducible Factor-1α, Causing Glycolysis Shutdown and Cell Death Cancer Research. ,vol. 65, pp. 999- 1006 ,(2005)
Ignacio Dolado, Aneta Swat, Nuria Ajenjo, Gabriella De Vita, Ana Cuadrado, Angel R. Nebreda, p38α MAP Kinase as a Sensor of Reactive Oxygen Species in Tumorigenesis Cancer Cell. ,vol. 11, pp. 191- 205 ,(2007) , 10.1016/J.CCR.2006.12.013
Takafumi HIRATA, Mitsuaki WATANABE, Shinji MIURA, Katsushi IJICHI, Masashi FUKASAWA, Ryuzo SAKAKIBARA, Inhibition of Tumor Cell Growth by A Specific 6-Phosphofructo-2-kinase Inhibitor, N-Bromoacetylethanolamine Phosphate, and Its Analogues Bioscience, Biotechnology, and Biochemistry. ,vol. 64, pp. 2047- 2052 ,(2000) , 10.1271/BBB.64.2047
G.-L. Wang, Liver tumors escape negative control of proliferation via PI3K/Akt-mediated block of C/EBPα growth inhibitory activity Genes & Development. ,vol. 18, pp. 912- 925 ,(2004) , 10.1101/GAD.1183304
Kartik Shankar, Vishal S Vaidya, Udayan M Apte, Jose E Manautou, Martin JJ Ronis, Thomas J Bucci, Harihara M Mehendale, Type 1 Diabetic Mice Are Protected from Acetaminophen Hepatotoxicity Toxicological Sciences. ,vol. 73, pp. 220- 234 ,(2003) , 10.1093/TOXSCI/KFG059
Pedro Vizan, Laszlo G. Boros, Agnes Figueras, Gabriel Capella, Ramon Mangues, Sara Bassilian, Shu Lim, Wai-Nang P. Lee, Marta Cascante, K-ras Codon-Specific Mutations Produce Distinctive Metabolic Phenotypes in Human Fibroblasts Cancer Research. ,vol. 65, pp. 5512- 5515 ,(2005) , 10.1158/0008-5472.CAN-05-0074