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. Author manuscript; available in PMC: 2018 Feb 10.
Published in final edited form as: Nature. 2017 Aug 2;548(7666):239–243. doi: 10.1038/nature23297

Figure 3. Hyperactive MAPK signalling triggers bronchiolar carcinoma by transdifferentiation of club cells.

Figure 3

a, Haematoxylin and eosin staining of paraffin-embedded sections showing the presence of intrabronchiolar carcinoma in Ad-Cre-infected Kras+/LSLG12Vgeo;Braf lox/LSLD631A (KBL) mice killed at humane end point. Two different magnifications are shown. Scale bar, 200 μm (top) and 50 μm (bottom). b, Representative immunostaining of paraffin-embedded sections showing intrabronchiolar tumours from Ad-Cre-infected Kras+/LSLG12Vgeo;Braf lox/LSLD631A (KBL, n = 5) mice using antibodies against, SPC, CC10, Ttf1, Sox2, p63 and Ck5. Scale bar, 50 μm. c, Immunostaining of paraffin-embedded consecutive sections showing early intrabronchiolar lesions (1 week after Ad-Cre infection) in Kras+/LSLG12Vgeo;Braf lox/LSLD631A (KBL) mice using antibodies against SPC and CC10. Arrowheads indicate protruding bronchiolar papillary growth undergoing transdifferentiation. Scale bar, 50 μm. d, Representative haematoxylin and eosin staining of paraffin-embedded lung sections (n = 3 per genotype) from Kras+/LSLG12Vgeo (K), Kras+/LSLG12Vgeo; Braf +/LSLD631A (KB) and Kras+/LSLG12Vgeo;Braf lox/LSLD631A (KBL) mice killed 2 months after infection with cell-type-restricted Ad-Cre viruses that selectively induce Cre-mediated recombination in AT2 (Ad-SPC-Cre) (top) and club cells (Ad-CC10-Cre) (bottom). Scale bar, 500 μm. Insets show high-magnification images. Scale bar, 100 μm. e, SPC and CC10 immunostaining of paraffin-embedded consecutive sections showing intrabronchiolar tumours from Kras+/LSLG12Vgeo;Braf lox/LSLD631A (KBL) mice infected with lineage-specific Ad-CC10-Cre. Scale bar, 100 μm.