Figure 1
MMA prevents doxycycline-induced pathological changes in the lungs of bitransgenic mice. (a) Doxycycline-induced lung tumor formation accompanied by increases in Sp1 and Kras in bitransgenic mice. After treatment for 1–5 months, lungs were excised for paraffin sections. Sections were prepared for hematoxylin and eosin (HE) staining and Sp1, Kras, pErk, proliferating cellular nuclear antigen (PCNA) and CCSP immunohistochemical staining. Stained sections were visualized using light microscopy ( × 200). (b) On each excised lung, surface pulmonary tumor nodules were counted. One spot represents one mouse. (c) After IHC staining, the Sp1 signal on each slide was semiquantitated by H-score. (d) After doxycycline treatment, lungs were collected for protein extraction, and analyzed by western blotting with anti-Kras and Sp1 antibodies. Data of eight independent experiments are represented as mean±s.e.m. (*P<0.05). (e) Prevention of Kras-induced lung tumorigenesis under the control of doxycycline by MMA. (Upper panel) Time course of doxycycline and MMA treatment. (Lower panel) HE and IHC staining using anti-Sp1 and Kras antibodies of lungs from treated bitransgenic mice. (f) After doxycycline administration for 5 months with MMA treatment in the last 2 months, lungs were excised from mice and pulmonary tumor nodules were counted. (g) H-score for the Sp1 signal on each slide. (h) MMA treatment attenuated Sp1 upregulation in Kras-induced lung tumorigenesis. pSp1 represents phosphorylated Sp1 and data of eight independent experiments are represented as mean±s.e.m. (*P<0.05).
