Fig. 1

Heterozygous germline deletion of Brca1 in p18-deficient mice activates EMT with increase of Pdgfrβ in mammary tumors. a Summary of mammary tumors in mice with Balb/c background. Metastasis was found in the lung. EMT + tumors are defined as tumors that exhibit two of the following: decreased E-Cad, increased Vim, Fn1, or Cd29, and are positive for two EMT-transcription factors (Twist, Snail, Slug, Foxc2, or Fra1) in > 2% of cells. Pdgfrβ+ tumors are tumors that are positive for Pdgrfβ in > 2% tumor cells. The asterisk (*) denotes a significance from p18^−/−;Brca1^+/− and p18^−/− tumors by a two-tailed Fisher’s exact test. b Microarray analysis of tumors. Boxplot showing relative Pdgfrβ mRNA levels in p18^−/−;Brca1^+/− (n = 11) and p18^−/− (n = 9) tumors. c Representative immunostaining of mammary tumors from a p18^−/− and two p18^−/−;Brca1^+/− mice. Note that p18^−/−;Brca1^+/− tumor cells that invade into surrounding muscle are strongly positive for Pdgfrβ (tumor B in top panel) and that most Pdgfrβ-positive cells in p18^−/− tumors are stromal cells (tumor B in bottom panel). Pdgfrβ-positive p18^−/−;Brca1^+/− tumor cells at the tumor invasion front are indicated. d–f X-Y plot showing the relation of Pdgfrβ mRNA and ssGSEA enrichment scores for signatures of Pdgf signaling activity [55] (d), EMT in breast cancers [56] (e), and mammary stem cells [57] (f)