Context-Dependent Effects of Amplified MAPK Signaling during Lung Adenocarcinoma Initiation and Progression.
Cell Rep
; 18(8): 1958-1969, 2017 02 21.
Article
in En
| MEDLINE
| ID: mdl-28228261
ABSTRACT
Expression of oncogenic KrasG12D initiates lung adenomas in a mitogen-activated protein kinase (MAPK) signal-dependent manner from only a subset of cell types in the adult mouse lung. Amplification of MAPK signaling is associated with progression to malignant adenocarcinomas, but whether this is a cause or a consequence of disease progression is not known. To better understand the effects of MAPK signaling downstream of KrasG12D expression, we capitalized on the ability of Braf inhibition to selectively amplify MAPK pathway signaling in KrasG12D-expressing epithelial cells. MAPK signal amplification indeed promoted the rapid progression of established adenomas to malignant adenocarcinomas. However, we observed, surprisingly, a greater number of overall tumor-initiating events after MAPK signal amplification, due to induced proliferation of cell types that are normally refractory to KrasG12D-induced transformation. Thus, MAPK signaling in the lung is thresholded not only during malignant progression but also at the moment of tumor initiation.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Adenocarcinoma
/
Signal Transduction
/
Cell Transformation, Neoplastic
/
Mitogen-Activated Protein Kinases
/
Lung Neoplasms
Limits:
Animals
Language:
En
Journal:
Cell Rep
Year:
2017
Document type:
Article
Affiliation country:
United States