Fig. 3. Endometrial tumor development is estrogen dependent in Smad2/3 cKO mice.

a–d Gross uteri from adult control (a, c) and Smad2/3 cKO mice (b, d) collected 3 months after ovariectomy (OVX) and treated without (a, b) or with estradiol releasing pellets (c, d). Only the Smad2/3 cKO mice that received the estradiol treatment developed tumors. e–h H&E stained uterine cross-sections stained of control (e, g) and Smad2/3 cKO (f, h) that were ovariectomized and treated without (e, f) or with estradiol (g, h). i–t Immunostaining of control (i, j, m, n, q, r) and Smad2/3 cKO mice (k, l, o, p, s, t) cross sections following OVX + E2 treatment. i–l Tissue sections were stained with the epithelial cell marker, E-cadherin (CDH1, green) and smooth muscle actin (SMA, red). Compared to controls (i, j) sections from Smad2/3 cKO mice (k, l) show disordered epithelial cell and smooth muscle layers. m–p Tissue sections were stained with E-cadherin (CDH1, green) and progesterone receptor (PR, red). PR can be seen in the nuclei of the control mice (m, n) but not in the epithelium of Smad2/3 cKO mice (o, p). q–t Uterine cross sections were stained with E-cadherin (CDH1, red) and estrogen receptor α (ERα, green) antibodies. Cross sections from control (q, r) and Smad2/3 cKO (s, t) mice were positive for ERα. Nuclei were stained with DAPI (white). H&E and immunostaining experiments were performed in samples from at least 3 control and 3 Smad2/3 cKO mice.