Figure 7. Clims promote the initiation and progression of tumors in the MMTV-PyMT breast cancer mouse model.

(A–B) Expression of (A) Clim2 and (B) Clim1 in the molecular subtypes of breast cancer. Clim2 is more highly expressed in less differentiated Claudin-low (CLow) and basal-like (BasL) tumor subtypes and Clim1 is more highly expressed in the differentiated Luminal A and B (LumA and LumB) subtypes. (C) Survival analysis within the UNC 337 cohort of breast cancer patients grouped by median expression of Clim1 and Clim2 demonstrates worse prognosis in patients with highest expression of Clim1/2. (D) DN-Clim prevents tumorigenesis in the PyMT tumor model as determined by quantification of the number of mammary glands with palpable tumors. Data represent mean ± SEM from ten mice of each genotype. (E) DN-Clim expression in the PyMT tumor model significantly delays development of palpable tumors. In PyMT mice, the second palpable tumor is detected within a few days of the first tumor, but when DN-Clim is expressed there is a significant increase in the time to detect the second palpable tumor. P-values derived from Log-rank test. (F) Decreased rate of tumor progression in DN-Clim/PyMT mice. P-values derived from repeated measures ANOVA. (G) Representative whole mounts of PyMT tumors with or without DN-Clim suggest a function for Clim in the tumor initiation stages. The primary tumor was excised from three month old mice before whole mount of the mammary gland. (H) K8, K14, and Myc-tag (DN-Clim) expression in mammary glands from 6 week old PyMT mice with or without DN-Clim. High K8 and low K14 expression demonstrate the luminal subtype features of PyMT tumors. DN-Clim expression is observed in basal cells of the tumor.