1. Deletion of Lats1 is phenotypically distinct from Lats2 deletion in PyMT tumors.
Deletion of Lats1 is phenotypically distinct from Lats2 deletion in PyMT tumors. (A) Relative tumor weight, as percentage of total body weight, in three month old Lats1-CKO PyMT and WT-PyMT littermate controls (n = number of mice); mean ± SEM; *P-value < (B) Three mammary glands from Lats1-CKO PyMT and WT-PyMT littermate controls were histologically scored and tallied. Right panel: representative H&E-stained adenosquamous carcinoma sample from a Lats1-CKO PyMT tumor (scale bar = 200 μm). (C) Immunohistochemistry analysis of ERα protein expression in tumors from 3-mo-old Lats1-CKO PyMT and WT-PyMT littermate controls. Left panel: two representative tumor sections from each genotype (scale bar = 100 μm). Right panel: mean ± SEM of % ER+ cells in tumors from eight Lats1-CKO PyMT and 6 WT-PyMT mice; *P-value < (D) Immunohistochemistry analysis of CK14, performed as in (C). Right panel depicts mean ± SEM of percentage of slide area with intense membranous CK14 staining in the invasive front of the tumor; *P-value < (E) Heatmap representing hierarchical clustering of global expression patterns of tumors from 3-mo-old Lats1-CKO PyMT and WT-PyMT littermate controls. Standardized rld values are shown for differentially expressed genes (P-value < 0.05, n = 2029). ad = adenoma/MIN, car = carcinoma, asc = adenosquamous carcinoma; (F) Left panel: GSEA assessing PPARγ transcriptional activity in Lats1-CKO PyMT versus Lats2-CKO PyMT tumors. Genes differentially expressed (adjP-value < 0.05) in either Lats1-CKO PyMT (compared with littermate controls) or Lats2-CKO PyMT (compared with littermate controls) were ranked according to fold change differences (log ratio) and compared with a gene set comprising PPARγ target genes (El Akoum, 2014). Right panel: box plot representing mean fold change (log 2) of genes comprising the PPAR pathway (KEGG database) in Lats1-CKO PyMT and Lats2-CKO PyMT, each compared with their WT-PyMT littermate controls. Only genes with P-value of comparison < 0.05 were included; ***P-value <
Noa Furth et al. LSA 2018;1:e
© 2018 Furth et al.