English version ENG

Program: Resurse umane

Tipul de proiect: Proiecte de cercetare pentru stimularea constituirii de tinere echipe de cercetare independente 

 

Aceasta cercetare a fost finantata de un grant al Autoritatii Nationale de Cercetare Stiintifica din Romania, CNCSUEFISCDI

 

Titlul: Efectul polifenolilor in modularea relatiei dintre proteinele ErbB si ciclul celular in progresia adenocarcinomului mamar si epidermoid

 

Numar proiect: PN-II-RU-TE-2011-3-0204

Contract: 111/10.10.2011

Durata: 36 luni

Data de incepere a proiectului: 10.10.2011

Data de finalizare a proiectului: 10.09.2014

 

Rezumat

 

Proteinele ErbB, membri ai familiei receptorilor tirozin kinazici (RTK), si caile acestora de semnalizare au un rol important in migrarea, adeziunea, apoptoza si proliferarea celulara. In celulele tumorale expresia, interactiunile si semnalizarea prin intermediul proteinelor ErbB in mod frecvent nu sunt strict organizate asa cum se observa in conditii fiziologice. Studii recente au indicat RTK ca fiind una dintre tintele critice ale actiunii polifenolilor in diminuarea proliferarii celulelor tumorale. In cadrul acestui proiect ne propunem sa investigam efectul polifenolilor asupra progresiei ciclului celular si apoptozei in corelatie cu nivelul de expresie, interactiunea, activarea si caile de semnalizare ale proteinelor ErbB in liniile celulare de adenocarcinom mamar si epidermoid. Ne propunem sa corelam acesti parametri cu tipurile si concentratiile de polifenoli. Pentru experimente vom folosi in principal citometria in flux care furnizeaza date statistice robuste. Interactia dintre proteinele ErbB va fi investigata atat prin metode de imunofluorescenta cu ajutorul microscopului confocal (co-localizare), cat si cu ajutorul metodei FCET (flow cytometric fluorescence resonance energy transfer). Starea de activare a proteinelor ErbB si a cailor acestora de semnalizare (de exemplu: PI3K sau Akt) vor fi investigate cu ajutorul metodei western blot. Ne asteptam ca acest proiect sa clarifice rolul polifenolilor la nivelul proteinelor ErbB si sa contribuie la stabilirea rolului polifenolilor in terapia si chemopreventia cancerului.

Cuvinte cheie: proteinele ErbB, polifenoli, celule tumorale, ciclul celular, apoptoza

 

Obiective

 

  • Studierea actiunii polifenolilor asupra progresiei ciclului celular, apoptozei, si viabilitatii celulare
  • Investigarea efectului polifenolilor asupra nivelului expresiei proteinelor ErbB
  • Studierea efectului polifenolilor asupra asocierii la nivel molecular a proteinelor ErbB
  • Investigarea corelatiei dintre activarea proteinelor ErbB si tratamentul cu polifenoli
  • Investigarea efectelor polifenolilor asupra cailor de semnalizare ale proteinelor ErbB

 

Activitati (.pdf)

 

Echipa:

Lecturer Dr. Mocanu Maria-Magdalena – principal investigator

Prof. Dr. Ganea Constanta – senior researcher

Assoc. Prof. Dr. Irina Baran – postdoctoral researcher

Laura Georgescu – student

Flavia Iacobescu – student

Rodica Zaharia – technical assistant

Elena Constantin – technical assistant 

 


Rapoarte de sinteza ale activitatii stiintifice: .pdf (romana)


Diseminarea rezultatelor:


 
Publicatii ISI:

  1. Mocanu Maria-Magdalena, Surcel Mihaela, Ursaciuc Cornel, Katona Eva, Ganea Constanta, Antiproliferative effect of quercetin in mammary and epidermoid cancer, ROMANIAN BIOTECHNOLOGICAL LETTERS 2013, vol. 18, no. 6, pp. 8796-8803,  (IF. 0.363)(is 0.115) [ link ]

  2. M.M. Mocanu, C. Ganea, L. Georgescu, T. Varadi, D. Shrestha, I. Baran, E. Katona, P. Nagy, J. Szöllösi, Epigallocatechin-gallate determines ErbB proteins downregulation, cell death mediated by 67kDa laminin receptor and altered lipid order in mammary and epidermoid carcinoma cells, 2013, J. NAT. PROD., DOI: 10.1021/np4007712
    data publicarii (Web): 23 ian, 2014,
    (IF. 3.285) (is. 1.867) [ link ]

  3. Mocanu MM, Ganea C, Siposova K, Filippi A, Demjen E, Marek J, Bednarikova Z, Antosova A, Baran I, Gazova Z, Polymorphism of lysozyme amyloid fibrils influences the cytotoxicity in LLC-PK1 epithelial kidney cells, 2013 – submis, INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES, Volume 65, April 2014, Pages 176-187, (IF. 2.596, is.0.618) [ link ]

Conferinte nationale si internationale cu comitet de program:

  1. Mocanu MM, Nagy P, Georgescu L, Varadi T, Shrestha D, Baran I, Katona E, Szollosi J, Ganea C, The effect of flavonoids in mammary and epidermoid tumor cells with ErbB proteins overexpression, oral communication, 8th International Conference "Structure and Stability of Biomacromolecules" (SSB 2013), September 10-13, 2013, Kosice, Slovakia

  2. Mocanu MM, Ganea C, Siposova K, Fillipi A, Radu E, Demjen E, Marek J, Bednarikova Z, Antosova A, Gazova Z, Distinct fibrils morphology induces different cytotoxicity in renal cells 8th International Conference "Structure and Stability of Biomacromolecules" (SSB 2013), September 10-13, 2013, Kosice, Slovakia

  3. Gazova Z, Siposova K, Filippi A, Demjen E, Marek J, Ganea C, Mocanu MM, Polymorphism of lysozyme amyloid fibrils and cell viability, poster, 9th European Biophysics Congress (EBSA2013), July 13-17, 2013 Lisbon, Portugal

  4. M.M. Mocanu, E. Katona, M. Surcel, L. Georgescu, T. Varadi, I. Baran, P. Nagy, C. Ursaciuc, J. Szöllősi, C. Ganea, Effect of flavonoids on cell cycle and apoptosis in tumor cell lines overexpressing ErbB proteins, oral communication, 9th National Congress of Cytometry, May 16-18, 2013, Bucharest, Romania

  5. Z. Gazova, K. Siposova, M. Koneracka, V. Zavisova, A. Filippi, D. Ionescu, P. Kopcansky and M.M. Mocanu, Anti-amyloid effect of magnetic fluid in vitro and in cells, poster, 13th International Conference on Magnetic Fluid, January 7-11, 2013, New Dehli, India

  6. Gazova Z., Siposova K., Koneracka M., Zavisova V., Kopcansky P., Filippi A., Ganea C., Baran I., Mocanu M.M., Magnetic fluids attenuate the cytotoxic effect of amyloid fibrils, poster, 22nd IUBMB & 37th FEBS Congress, September 4 - 9, 2012, Sevilla, Spania

  7. M. M. Mocanu, K. Siposova, C. Ganea, I. Baran, A. Antosova, Z. Gazova, Protective role of nanoparticles against cytotoxic effect induced by amyloid fibrils, XXIII Biochemical Congress, August 26-29, 2012, Brno, Czech Republic

  8. M.M. Mocanu, C. Ganea, I. Baran, E. Katona, C. Ursaciuc, M. Surcel, P. Nagy, J. Szöllősi, Polyphenolic compounds induce the blockage of the cell cycle progression on tumor cell lines overexpressing ErbBs proteins, poster, ISAC XXVII International Congress, June 23 – 27, 2012, Leipzig, Germany

  9. M. M. Mocanu, K. Siposova, M. Muckova, J. Lazova, C. Ganea, I. Baran, Z. Gazova, Magnetic fluid reverses inhibition of cell growing caused by protein amyloid fibrils, 9th International Conference on the Scientific and Clinical Applications of Magnetic Carriers, May 22-26, 2012, Minneapolis, Minnesota, U.S.A.

  10. A. Filippi, K. Siposova, A. Nedelcu, C. Ursaciuc, M. Surcel, A. Antosova, Z. Gazova, M.M. Mocanu, Lysozyme amyloid fibrils induce apoptosis on LLC-PK1 cells, poster, 8th National Citometry Congress, May 10 – 11, 2012, Bucharest, Romania

 

Ultima actualizare: decembrie 2014
Acest site este actualizat la finalizarea fiecarei etape din desfasurarea proiectului si in momentul publicarii rezultatelor, articolelor, etc. Structura site-ului respecta recomandarile structurale ale CNCS (decembrie 2011)


Pentru orice informatii suplimentare:
Contact: Conf . dr. Magda Mocanu
UMF "Carol Davila" Bucuresti, Disciplina de Biofizica
Bd. Eroilor Sanitari nr 8
050474 Bucuresti, Romania
email: mmocanu [at] umf [dot] ro