Oncogenic K-ras drives cell cycle progression and phenotypic conversion of primary pancreatic duct epithelial cells

C Agbunag, D Bar-Sagi - Cancer research, 2004 - AACR
C Agbunag, D Bar-Sagi
Cancer research, 2004AACR
We have established a primary pancreatic duct epithelial cell culture (PDEC) system to
investigate the relationship between oncogenic activation of K-ras and pancreatic ductal
tumorigenesis. We have found that the acute introduction of physiological levels of
oncogenic K-ras (K-rasV12) into quiescent PDECs stimulates S-phase entry and induces a
pronounced increase in cell size. Both effects are dependent on the functional integrity of the
phosphatidylinositol 3′-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling …
Abstract
We have established a primary pancreatic duct epithelial cell culture (PDEC) system to investigate the relationship between oncogenic activation of K-ras and pancreatic ductal tumorigenesis. We have found that the acute introduction of physiological levels of oncogenic K-ras (K-rasV12) into quiescent PDECs stimulates S-phase entry and induces a pronounced increase in cell size. Both effects are dependent on the functional integrity of the phosphatidylinositol 3′-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling pathway. In addition, K-rasV12 promotes the loss of epithelial E-cadherin and the gain of mesenchymal N-cadherin in PDEC. Our observations indicate that the oncogenic activation of K-ras is sufficient to elicit mitogenic and morphogenic responses in pancreatic ductal cells and hence is likely to play an instructive role in the initiation of pancreatic ductal adenocarcinoma.
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