Oncogene

Un oncogene è un gene, o una serie di nucleotidi che codificano una proteina, che potenzialmente indirizza la cellula verso lo sviluppo di un fenotipo neoplastico. Solitamente gli oncogeni intervengono nello sviluppo tumorale e aumentano le possibilità che lo sviluppo (proliferazione e differenziamento) di una cellula si diriga in senso tumorale. Nuove ricerche indicano che piccoli RNA di 21-25 nucleotidi, detti miRNA, possono controllare tali geni attraverso la sottoregolazione.[senza fonte]

Il primo oncogene fu scoperto nel 1970 e chiamato Src (pronunciato SARC). Src fu scoperto dapprima in un retrovirus dei polli. Nel 1976 J. Michael Bishop e Harold E. Varmus dell'Università della California dimostrarono che questo oncogene era un difettoso proto-oncogene presente in numerosi organismi tra cui l'uomo. Per i loro studi Bishop e Varmus furono insigniti del Premio Nobel nel 1989.

Proto-oncogeni

Un proto-oncogene è un gene normale che può diventare oncogenetico a causa di mutazioni o di un aumento dell'espressione. I proto-oncogeni codificano proteine che regolano il ciclo cellulare, la sopravvivenza e il differenziamento cellulare. Possono anche essere coinvolti nella trasduzione del segnale di avvio della mitosi.

Attivazione

Un proto-oncogene diviene un oncogene anche con minime modificazioni delle sue funzioni originali. Ci sono due tipi fondamentali di attivazione:

  • Una mutazione dei nucleotidi producono una proteina diversa causando:
    • un aumento dell'attività (enzimatica) della proteina
    • la perdita dei siti di regolazione
    • la creazione di proteine ibride
  • Un aumento della concentrazione di proteine causata da

Oncogèni

Fattori di crescita

I fattori di crescita, o mitogeni, sono solitamente secreti in poche cellule specializzate per indurre la proliferazione in modo paracrino, autocrino, o endocrino. Se una cellula che normalmente non produce fattori di crescita improvvisamente incomincia a produrne (perché ha sviluppato un oncogene), questo induce la proliferazione, senza controllo, nelle cellule adiacenti (azione paracrina) e nello stesso suo tipo cellulare (azione autocrina) aumentando la secrezione.

Protein chinasi

Ci sono sei classi conosciute di protein chinasi e proteine correlate che sono potenziali oncogeni:

  1. Recettore tirosin-chinasico che diviene costitutivamente (permanentemente) attivato; ad esempio il Recettore per l’epidermal growth factor (EGFR), il Recettore per il platelet-derived growth factor (PDGFR), e il Recettore per il fattore di crescita dell'endotelio vascolare (VEGFR).
  2. Tirosin-chinasi citoplasmatica come ad esempio gli enzimi tirosin-chinasici della famiglia Src, Syk-ZAP-70 e BTK.
  3. GTPasi regolatoria come la Ras; mutazioni che attivano in modo permanente Ras si riscontrano nel 20-25% di tutti i tumori umani e fino al 90% in alcuni tipi di tumore, ad esempio pancreatici.
  4. Serin/Treonin chinasi citoplasmatica e sue unità regolatrici per esempio Raf chinasi, e Chinasi ciclina dipendente.
  5. Proteine adattatrici nella trasduzione del segnale (ad esempio nella via apoptotica)
  6. Fattori di trascrizione per esempio il gene Myc.

Voci correlate

Collegamenti esterni

Controllo di autoritàNDL (EN, JA) 01234791
  Portale Biologia

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