Fig. 6
fects of FASN deletion in tumor development. a FASN-stained slides from wild-type and MMTV-PyMT FVB mice mammary pads at weeks 4, 8, and 13. FASN is expressed in the cytoplasm of adipocytes (asterisks) in wild-type animals. A weaker FASN expression was observed in breast epithelial ducts (arrows). Conversely, FASN upregulation was observed in the proliferating ducts (week 4), invasive carcinomas arising from the ducts (week 8), and fully developed tumors (week 13) in the MMTV-PyMT animals. Scale bars, 100 μM. b Representative images of sections of the mammary pad of FASN+/+; PyMT and FASN∆/∆; PyMT animals stained for FASN. The areas negative for FASN have normal or at most proliferative (but not invasive) ducts (asterisks). Invasive growth was only observed in the FASN-positive areas of the FASN∆/∆; PyMT mice (arrows). Scale bars, 200 μm (low magnification) and 100 μm (high magnification; i, ii, iii). c Representative fluorescent images of DAPI (blue) and 8-oxo-deoxyguanosine (8-oxo-dG) (red) staining of mammary pad sections of FASN+/+; PyMT and FASN∆/∆; PyMT animals. Merged images are shown. The quantification of cellular 8-oxo-dG fluorescence intensity in breast tumors is shown on the right (FASN+/+; PyMT, n = 4500 cells; FASN∆/∆; PyMT, n = 6500 cells). Presented data are the mean values ± SD. ***P < 0.001; Student’s t test. Scale bars, 50 μM. d Representative fluorescent images of DAPI (blue), FASN (green), and 8-oxo-dG (red) co-staining of mammary pad section of FASN∆/∆; PyMT animals. Scale bars, 50 μM. e Time to killing due to loco-regional tumor growth of FASN+/+; PyMT (n = 43) and FASN∆/∆; PyMT (n = 44) animals; survival is increased from 90 to 123 days (log-rank P < 0.0001). f Tumor volume evolution in FASN+/+; PyMT (n = 43) and FASN∆/∆; PyMT (n = 44) animals. Representative tumor burden charts at T4, T5, and T6 weeks (since treatment initiation) are shown below the survival curve (T4: FASN+/+; PyMT n = 42, FASN∆/∆; PyMT n = 16; T5: FASN+/+; PyMT n = 41, FASN∆/∆; PyMT n = 15; T6: FASN+/+; PyMT n = 40, FASN∆/∆; PyMT n = 15). Presented data are the mean values ± SEM. ***P < 0.001; Student’s t test
