Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=28752115
&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215
Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\28752115
.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Cell+Mol+Gastroenterol+Hepatol
2017 ; 4
(2
): 263-282
Nephropedia Template TP
Chuvin N
; Vincent DF
; Pommier RM
; Alcaraz LB
; Gout J
; Caligaris C
; Yacoub K
; Cardot V
; Roger E
; Kaniewski B
; Martel S
; Cintas C
; Goddard-Léon S
; Colombe A
; Valantin J
; Gadot N
; Servoz E
; Morton J
; Goddard I
; Couvelard A
; Rebours V
; Guillermet J
; Sansom OJ
; Treilleux I
; Valcourt U
; Sentis S
; Dubus P
; Bartholin L
Cell Mol Gastroenterol Hepatol
2017[Sep]; 4
(2
): 263-282
PMID28752115
show ga
BACKGROUND & AIMS: Transforming growth factor beta (TGF?) acts either as a tumor
suppressor or as an oncogene, depending on the cellular context and time of
activation. TGF? activates the canonical SMAD pathway through its interaction
with the serine/threonine kinase type I and II heterotetrameric receptors.
Previous studies investigating TGF?-mediated signaling in the pancreas relied
either on loss-of-function approaches or on ligand overexpression, and its
effects on acinar cells have so far remained elusive. METHODS: We developed a
transgenic mouse model allowing tamoxifen-inducible and Cre-mediated conditional
activation of a constitutively active type I TGF? receptor (T?RI(CA)) in the
pancreatic acinar compartment. RESULTS: We observed that T?RI(CA) expression
induced acinar-to-ductal metaplasia (ADM) reprogramming, eventually facilitating
the onset of KRAS(G12D)-induced pre-cancerous pancreatic intraepithelial
neoplasia. This phenotype was characterized by the cellular activation of
apoptosis and dedifferentiation, two hallmarks of ADM, whereas at the molecular
level, we evidenced a modulation in the expression of transcription factors such
as Hnf1?, Sox9, and Hes1. CONCLUSIONS: We demonstrate that TGF? pathway
activation plays a crucial role in pancreatic tumor initiation through its
capacity to induce ADM, providing a favorable environment for
KRAS(G12D)-dependent carcinogenesis. Such findings are highly relevant for the
development of early detection markers and of potentially novel treatments for
pancreatic cancer patients.
free
free
free
