Multiple cells-of-origin of mutant K-Ras-induced mouse lung adenocarcinoma
Kate D Sutherland, Ji-Ying Song, Min Chul Kwon, Natalie Proost, John Zevenhoven, Anton Berns
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | NATL ACAD SCIENCES | Published : 2014
Much controversy surrounds the cell-of-origin of mutant K-Ras (K-RasG12D)-induced lung adenocarcinoma. To shed light on this issue, we have used technology that enables us to conditionally target K-RasG12D expression in Surfactant Protein C (SPC)(+) alveolar type 2 cells and in Clara cell antigen 10 (CC10)(+) Clara cells by use of cell-type-restricted recombinant Adeno-Cre viruses. Experiments were performed both in the presence and absence of the tumor suppressor gene p53, enabling us to assess what effect the cell-of-origin and the introduced genetic lesions have on the phenotypic characteristics of the resulting adenocarcinomas. We conclude that both SPC-expressing alveolar type 2 cells a..View full abstract
Awarded by National Health and Medical Research Council of Australia Overseas-based Biomedical Training Fellowship
We thank E. Riem and J. van Ooij for their expert technical assistance, the personnel of the animal facility for this excellent animal husbandry, P. Krimpenfort and J. Vissers for critically reading the manuscript, and R. van Amerongen for advice regarding the imaging of R26R-Confetti multicolor reporter animals. We thank Tyler Jacks for providing the K-Ras<SUP>LSL-G12D/+</SUP> mice. We acknowledge B. Stripp for providing us with the anti-CCSP antibody. K.D.S. was a recipient of a National Health and Medical Research Council of Australia Overseas-based Biomedical Training Fellowship (No. 516781). This work was supported by a program grant of the Dutch Cancer Society and by funds provided by the European Platform for Translational Cancer Research consortium.