Figure 1.
Average blood glucose levels in WT and K-RasV12 mice before and after STZ treatment.
Tail-vein glucose was measured after 3 hours of fast. Mean ± standard error of mean; *p<0.05 versus untreated-K-RasV12; **p<0.05 versus untreated-WT (Student's t-test).
Figure 2.
Histology and immunostaining of pancreas in treated and untreated mice with STZ. A.
(i, iv) H-E of a pancreatic islet in untreated and STZ-WT mice; (ii, v) and (iii,vi) reduction of Glut2 and insulin expression in STZ-WT mice compared to control mice. B. (i, iv) H–E of a pancreatic islet in untreated and STZ-K-RasV12 mice; (ii, v) and (iii,vi) reduction of Glut2 and insulin expression in STZ-K-RasV12 mice compared to untreated K-RasV12 control mice. Magnification 200×. Calibration bar: 50 µm.
Figure 3.
Early and late time representation of tumor formation and progression, respectively.
A. Early time, after 4 weeks from STZ treatment, no tumor formation in untreated-K-RasV12 mice (i) and some tumors in K-RasV12 mice treated with STZ (ii). B. Late time, after 24 weeks from STZ treatment, well defined masses in untreated-K-RasV12 mice (i) and several multifocal tumor distribution in K-RasV12 treated with STZ (ii). C. Assessment of tumors at low and high grade in untreated-K-RasV12 and STZ- K-RasV12. Left: percent of low (white bar) and high (black bar) tumors in STZ- K-RasV12 and untreated-K-RasV12 mice (mean ± SEM; *, p<0.01 by X2 test). Right: representative H-E of low and high lung tumor grade. H-E, magnification 100×. Calibration bar: 100 µm.
Figure 4.
Assessment of tumor development and progression of lung tumors in STZ-K-RasV12 mice compared to untreated-K-RasV12 ones.
A. Average number of tumors that developed per mouse in STZ-K-RasV12 (black bar) compared to untreated-K-RasV12 (white bar) mice. B. Average tumor size (mm2) in STZ-K-RasV12 (black bar) and in untreated-K-RasV12 mice (white bar). C. Expression of neoplastic tissue with the tumor burden index which considers average number of tumors per mice and average size. Data are presented as mean ± SEM, *p<0.05 (Student's t-test).
Figure 5.
A. Immunohistochemical analysis of CC10 and SP-C in terminal bronchioles of STZ-K-RasV12 (i, ii) and untreated-K-RasV12 (iii, iv) mice. Magnification 200×. Calibration bar: 50 µm. B. Bar graph indicates percentage of terminal bronchioles with 1 or more BASCs at early and late time (STZ-K-RasV12 vs STZ-WT: *p<0,01 by X2 test).
Figure 6.
Immunofluorescent staining of tissue sections to detect the Glut1 expression (red).
A. Terminal bronchioles of both STZ-K-RasV12 and untreated-K-RasV12 mice; B. Tumoral masses of STZ-K-RasV12 mice. Magnification 100×. Calibration bar: 100 µm.
Figure 7.
Oncogenic K-Ras induces Glut1 expression in BASCs.
A. Immunofluorescent analysis of CC10 (green) and SP-C (red) dual positive BASCs of K-Ras (+/LSLG12Vgeo); RERTn (ert/ert) mice after 4-OHT treatment in vitro. B. Spheres from K-Ras (+/LSLG12Vgeo); RERTn (ert/ert) mice treated with 4-OHT in vitro show β-Gal staining and Glut1 expression compared with no Glut1 staining in control spheres from K-Ras (+/LSLG12Vgeo); RERTn (ert/ert) mice not treated with 4-OHT. Magnification 200×. Calibration bar: 50 µm.