Fig. 1: Deregulated Myc combination with delated Pten in mammary gland accelerates triple-negative mammary tumorigenesis.

A Copy number alteration (CNA) in MYC showing amplification or gain and PTEN showing shallow or deep deletion and B mRNA expression of MYC and PTEN in 309 ER−/HER2− patients from 2500 breast cancer patients—METABRIC Data³¹ (* represent significant two-tailed p value < 0.05, n.s represent a non-significant p value). C Total 101 PTEN deletion in 309 ER-/HER2- patients with 77% MYC amplification or gain; the rest, 198 ER-/HER2- PTEN diploid patients, with 45% MYC amplification or gain, (two-tailed p value = 0.001). D Survival in 101 ER−/HER2− patients from METABRIC Data with PTEN loss and with (red dotted line) or without (green line) MYC amplification or gain (p value = 0.0187 using Gehan–Breslow–Wilcoxon test). E Diagram for generation of Myc;Ptenfl (Rosa;^{LSL-Myc/LSL-Myc}Pten;^fl/flBlg-Cre) mice by breeding the Rosa^{LSL-Myc/LSL-Myc} conditional knockin and Pten^fl/fl conditional knock-out mice with Blg-Cre transgenic mice. F Mammary gland tumor incidence from Myc (Rosa;^{LSL-Myc/LSL-Myc}Blg-Cre), Ptenfl (Pten;^fl/flBlg-Cre) and Myc;Ptenfl mice post-breeding and lactation for Blg-Cre activation (p value = 0.00001 using Gehan–Breslow–Wilcoxon test). Myc;Ptenfl (N = 26), Ptenfl (N = 10), and Myc (N = 15). G H&E staining for Myc;Ptenfl tumors, and Immunohistochemistry staining with anti-PR, anti-HER2, and Anti-estrogen receptor a (ERa). Representative images of 27 mammary gland tumors from Myc;Ptenfl mice and 10 tumors from Ptenfl mice. Scale bar = 100 µm. H Representative H&E staining for macro lymph node and lung metastases and micro lung metastasis from 38 Myc;Ptenfl mice and 19 Ptenfl mice. Metastasis rates: Ptenfl: 3/19 = 16%. Myc;Ptenfl stromal-rich: Macro 9/23 = 39%; Micro 3/23 = 13%. Myc;Ptenfl stromal-poor: Macro 5/15 = 33.3%; Micro 4/15 = 26.7%. Scale bars = 1 mm (Top), 200 µm (middle), 100 µm (bottom).