Journal article
Cell of origin of small cell lung cancer: Inactivation of Trp53 and Rb1 in distinct cell types of adult mouse lung
KD Sutherland, N Proost, I Brouns, D Adriaensen, JY Song, A Berns
Cancer Cell | CELL PRESS | Published : 2011
Abstract
Small cell lung cancer (SCLC) is one of the most lethal human malignancies. To investigate the cellular origin(s) of this cancer, we assessed the effect of Trp53 and Rb1 inactivation in distinct cell types in the adult lung using adenoviral vectors that target Cre recombinase to Clara, neuroendocrine (NE), and alveolar type 2 (SPC-expressing) cells. Using these cell type-restricted Adeno-Cre viruses, we show that loss of Trp53 and Rb1 can efficiently transform NE and SPC-expressing cells leading to SCLC, albeit SPC-expressing cells at a lesser efficiency. In contrast, Clara cells were largely resistant to transformation. The results indicate that although NE cells serve as the predominant ce..
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Awarded by National Institutes of Health
Funding Acknowledgements
We thank J. Zevenhoven, E. Riem, and J. van Ooij for their expert technical assistance; R. Kerkhoven for his expert help with performing array CGH analysis, and E. van Montfort for his assistance in interpreting the data; the personnel of the animal facility for their excellent animal husbandary; M. C. Kwon and P. Krimpenfort for critically reading the manuscript. We acknowledge J. Calbo for providing us with the mSCLC clonal cell lines; B. Stripp for providing us with the anti-CCSP antibody, S. Glasser for providing us with the mouse SP-C promoter, and R. I. Linnoila for kindly providing us with the mouse CC10 promoter and the rascal construct. K.D.S was a recipient of a National Health and Medical Research Council of Australia Overseas based Biomedical Training Fellowship (No. 516781). I.B. and D.A. are supported by the Fund for Scientific Research-Flanders (No. G.0081.08). This work was also supported by a grant of the Dutch Cancer Society.