Mammary-specific inactivation of E-cadherin and p53 impairs functional gland development and leads to pleomorphic invasive lobular carcinoma in mice

DMM006395 Supplementary Material

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  • Supplemental Figure S1 -

    Fig. S1. Loss of E-cadherin is not tolerated in the mouse mammary gland. (A-D) Immune histochemistry of control (Cdh1F/F;Trp53F/F; A and C) and Wcre;Cdh1F/F (B and D) female mice. Shown are H&E, E-cadherin, cytokeratin (CK) 8 and CK14 stainings. Mammary glands did not show abnormalities in virgin (A and B), or at day 17 of pregnancy (DP17) mice (C and D). Original magnification, (200X).

  • Supplemental Figure S2 -

    Fig. S2. Inactivation of E-cadherin and p53 inhibits lactation and nursing. Pups were fostered by their Wcre;Cdh1F/F;Trp53F/+ dam (black bars) or by a lactating wildtype control dam (white bars). Weight was measured and plotted longitudinally. As a control, we determined the average weight of pups from wildtype control females (grey bars). Error bars represent s.e.m. Statistical significance was determined using a two-tailed Student's T-Test. †=mice died after measurements.

  • Supplemental Figure S3 -

    Fig. S3. Inactivation of E-cadherin and p53 impairs alveo-lobular development during gestation. Comparative histochemistry showing E-cadherin expression in mammary glands from during pregnant (DP17) Wcre;Cdh1F/F;Trp53F/F mice and control (Cdh1F/F;Trp53F/F) animals. Note the loss of E-cadherin expression in the aberrant lobulo-alveolar structures (arrow) in contrast to typical expression of E-cadherin in the normal ductal and lobular structures (arrow head). Original mouse identification numbers are shown in the right bottom corner and may be cross-referenced with Supplementary Table S1. DP=Day of Pregnancy. Original magnification, (400X).

  • Supplemental Figure S4 -

    Fig. S4. Estrogen receptor expression in mammary tumors from the Wcre;Trp53F and Wcre;Cdh1F;Trp53F mouse models. Nuclear expression of estrogen receptor (ER) in mammary tumors. (A) ER expression on a Wcre;Trp53F/F mammary tumor diagnosed as AC + SC/CS. (B) Weak ± and focal (f) ER expression on a Wcre;Cdh1F/+;Trp53F/F mammary tumor diagnosed as SC/CS. (C) Absence of ER expression. on a mILC (solid type) from a Wcre;Cdh1F/F;Trp53F/+ female mouse. D-E: A mixed mILC+SC/CS with focal (f) ER expression. (D) represents the SC/CS component, whereas (E) shows a typical mILC 'scar-type' lesion. (F) ER expression on a mILC from a Wcre;Cdh1F/F;Trp53F/F female mouse. ER expression is indicated by arrows; open arrowheads depict ±(f) ER expression and filled arrowheads point to (pre-existing) ductal structures. Original magnification, (200X).

  • Supplemental Figure S5 -

    Fig. S5. Comparative immune histochemistry of metastatic mILC. Expression of cytokeratin (CK) 8 (left panels), CK14 (middle panels) and Vimentin (right panels) by metastatic mILC. (A-C) Metastases from different mILCs to a regional inguinal (A), a draining axillary (B) and a distant caudal (C) lymph node (LN). MD=mammary duct. (D and E) Distant metastases to lung (D) and spleen (E). Note the abundant presence of stromal cells in (C) and (E). B=bronchus. Arrows point to metastatic mILC cells. Scale bars are 100 µm.

  • Supplemental Table S1 -

    Table S1. Comparative histochemistry of mammary tumors from the Wcre;Chd1F;Trp53F mouse model.

  • Supplemental Table S2 -

    Table S2. Tumor spectrum and incidence in the Wcre;Cdh1F;Trp53F mouse model.