A, B BNip3 protein expression during mammary tumorigenesis in MMTV-PyMT mice detected at the adenoma/MIN stage of progression (50–65 days of age, n = 4), early carcinoma stage of tumorigenesis (65–80 days of age), late carcinoma stage (80–95 days of age, n = 4), metastatic carcinoma (95–105 days of age, n = 4) and in lung metastases (95–105 days of age, n = 4). Scale bar is 100 μm.
C Kaplan–Meier survival curve of MMTV-PyMT mice with either a wild-type (blue, n = 11) or BNip3 null (red, n = 11) background. Median survival of wild-type mice was 104 days and 80 days for BNip3 null mice. Significance P < 0.0001.
D Primary mammary tumor weights at d80 in wild-type (n = 24) and BNip3 null mice (n = 21).
E Gradient echo MRI images of mammary tumors (red arrows indicate the presence of tumor) at imaging resolution of approximately 117 mm, and slice thickness 0.5 mm.
F, G Immunohistochemical staining for Ki67 in wild-type (n = 20) and BNip3 null (n = 20) tumor sections at d65. Scale bar is 50 μm. Red arrows indicate regions of ectopic proliferation.
H Growth rate of primary wild-type (blue) and BNip3 null (red) MECs in vitro at 20% or 1% oxygen, measured in triplicate experiments.
I Growth rate of parental BNip3 null MECs, untreated or expressing either control empty vector (+ Empty vector) or BNip3-expressing vector (+ BNip3-WT), measured in triplicate experiments.