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Publication : Cell of origin of small cell lung cancer: inactivation of Trp53 and Rb1 in distinct cell types of adult mouse lung.

First Author  Sutherland KD Year  2011
Journal  Cancer Cell Volume  19
Issue  6 Pages  754-64
PubMed ID  21665149 Mgi Jnum  J:173560
Mgi Id  MGI:5014452 Doi  10.1016/j.ccr.2011.04.019
Citation  Sutherland KD, et al. (2011) Cell of origin of small cell lung cancer: inactivation of Trp53 and rb1 in distinct cell types of adult mouse lung. Cancer Cell 19(6):754-64
abstractText  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 cell of origin of SCLC a subset of SPC-expressing cells are also endowed with this ability.
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