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Table 1 Specific deletion of Brca1 induces mammary tumors with activation of Pdgfrβ signaling in p18- and p16-deficient mice

From: PDGFRβ is an essential therapeutic target for BRCA1-deficient mammary tumors

Genotype1

Mammary tumor #

Metastatic tumor #3

EMT+ tumor #4

Pdgfrβ+ tumor #5

p-Pkcα+ tumor #6

p-Fra1+ tumor #6

WT

0/9

     

p18−/−

7/15 (47%)

0/7

2/7 (29%)

2/7 (29%)

2/7 (29%)

2/7 (29%)

Brca1MGKO2

1/13 (8%)

0/1

1/1

1/1

1/1

1/1

p18-/-;Brca1MGKO

11/15 (73%)

4/11 (36%)

9/11 (82%)*

9/11 (82%)*

9/11 (82%)*

9/11 (82%)*

p16-/-

0/20

     

p16-/-;Brca1MGKO

6/10 (60%)

3/6 (50%)

6/6 (100%)

6/6 (100%)

6/6 (100%)

6/6 (100%)

  1. 1All mice were in Balb/c-B6 mixed background
  2. 2Brca1MGKO, Brca1f/f;MMTV-Cre, or Brca1f/-;MMTV-Cre
  3. 3Metastasis was found in the lung
  4. 4At least two EMT markers (decreased E-Cad, increased Vim, Fn1, Sma or Cd29) or two EMT-TFs, which included Twist, Slug, Snail, Foxc1, and Foxc2, were detected in > 2% tumor cells by IHC
  5. 5Tumors that had > 2% positive Pdgfrβ cells by IHC, or primary p18-/-;Brca1MGKO and p16-/-;Brca1MGKO tumor cells at passage 1 expressed fivefolds more Pdgfrβ than p18-/- tumor cells by western blot analysis (see Fig. 2e)
  6. 6Tumors that had > 2% positive p-Pkcα or p-Fra1 cells by IHC
  7. *A significance from p18-/-;Brca1MGKO and p18-/- tumors by a two-tailed Fisher’s exact test