Retinoid signaling in pancreatic cancer, injury and regeneration

Riferimento: 
PLoS One. 2011;6(12):e29075.
Autori: 
Colvin EK, Susanto JM, Kench JG, Ong VN, Mawson A, Pinese M, Chang DK, Rooman I, O'Toole SA, Segara D, Musgrove EA, Sutherland RL, Apte MV, Scarlett CJ, Biankin AV.
Fonte: 
PLoS One. 2011;6(12):e29075.
Anno: 
2011
Azione: 
Il segnalatore dei retinoidi sembra giocare un ruolo nella rigenerazione pancreatica e nella carcinogenesi, ma a differenza di cancro al seno, non è mediato direttamente dalla proteina cellulare di legame 1 dei retinoidi (CRBP1).
Target: 
Retinoidi/neoplasia pancreatica.

ABSTRACT
BACKGROUND
:
Activation of embryonic signaling pathways quiescent in the adult pancreas is a feature of pancreatic cancer (PC). These discoveries have led to the development of novel inhibitors of pathways such as Notch and Hedgehog signaling that are currently in early phase clinical trials in the treatment of several cancer types. Retinoid signaling is also essential for pancreatic development, and retinoid therapy is used successfully in other malignancies such as leukemia, but little is known concerning retinoid signaling in PC.
METHODOLOGY/PRINCIPAL FINDINGS:
We investigated the role of retinoid signaling in vitro and in vivo in normal pancreas, pancreatic injury, regeneration and cancer. Retinoid signaling is active in occasional cells in the adult pancreas but is markedly augmented throughout the parenchyma during injury and regeneration. Both chemically induced and genetically engineered mouse models of PC exhibit a lack of retinoid signaling activity compared to normal pancreas. As a consequence, we investigated Cellular Retinoid Binding Protein 1 (CRBP1), a key regulator of retinoid signaling known to play a role in breast cancer development, as a potential therapeutic target. Loss, or significant downregulation of CRBP1 was present in 70% of human PC, and was evident in the very earliest precursor lesions (PanIN-1A). However, in vitro gain and loss of function studies and CRBP1 knockout mice suggested that loss of CRBP1 expression alone was not sufficient to induce carcinogenesis or to alter PC sensitivity to retinoid based therapies.
CONCLUSIONS/SIGNIFICANCE:
In conclusion, retinoid signalling appears to play a role in pancreatic regeneration and carcinogenesis, but unlike breast cancer, it is not mediated directly by CRBP1.
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