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Blood, Vol. 112, Issue 4, 1357-1365, August 15, 2008
Inactivating Icmt ameliorates K-RAS–induced myeloproliferative disease
Blood Wahlstrom et al.
112: 1357
Supplemental materials for: Wahlstrom et al
Files in this Data Supplement:
- Figure S1. Lesions in multiple tissues of Icmtfl/flKLSLM mice show incomplete recombination of Icmt (JPG, 165 KB)
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(A-I) Hematoxylin- and eosin-stained sections of tissues from KLSLM, Icmtfl/+KLSLM, Icmtfl/flKLSLM, and control mice. (A) Normal thymus histology of a control mouse. (B) Malignant thymic lymphoma of a KLSLM mouse. (C) High-power view of panel B showing tumor cells with nuclear pleomorphisms and prominent nucleoli. (D) Normal lung histology of a control mouse. (E) Diffuse hyperplasia in lung of an Icmtfl/+KLSLM mouse. (F) Adenocarcinoma in the lung of an Icmtfl/flKLSLM mouse. (G) Papilloma in the forestomach of an Icmtfl/+KLSLM mouse (left); normal mucosa (right). (H, I) Papilloma in the rectoanal junction of a KLSLM mouse (H) and on the vulva of an Icmtfl/+KLSLM mouse (I). Magnification/numerical apertures of objectives used for the images in panels A, B, D, E, H, 20×/0.50; panel C, 100×/1.30 (+ oil); panel F, 40×/0.75; panel G, 10×/0.30; and panel I, 5×/0.15. (J) Genotyping of tissues and tumors from Icmtfl/flKLSLM mice by PCR amplification of genomic DNA.
- Figure S2. Analyses of RAS protein levels and activation of downstream effectors in unfractionated splenocytes (JPG, 77.7 KB)
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Western blots showing levels of GTP-bound and total RAS and phosphorylation of ERK and AKT in serum-starved and GM-CSF-stimulated unfractionated splenocytes. Experiments were performed with splenocytes from two mice of each genotype, with similar results.
- Figure S3. Inactivation of Icmt reduces lung tumor development in a second model of K-RAS–induced malignancies (JPG, 142 KB)
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Hematoxylin- and eosin-stained sections of lungs from 22–23 day-old mice. (A) Diffuse hyperplasia that obliterates alveolar spaces in lungs of an Icmtfl/+KLSLLC mouse. (B) Advanced adenoma of an Icmtfl/+KLSLLC mouse. The adenoma is compressing the surrounding areas of diffuse hyperplasia at left. (C) Adenocarcinoma in the lung shown in panel B showing a high degree of nuclear pleomorphism and variation in chromatin distribution, prominent nucleoli (arrows), and mitoses (arrowhead). (D) Lung from an Icmtfl/flKLSLLC mouse showing adenomatous and diffuse hyperplasia but with many areas of relatively normal histology. (E) High-power view of lung in panel D showing atypical adenomatous hyperplasia with moderate preservation of the alveolar architecture. (F) Normal lung histology of a control mouse. Magnification/numerical apertures of objectives used for images in panels A, D, F, 5×/0.15; panels B and E, 40×/0.75; and panel C, 63×/1.40 (+ oil).
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